Fat- and sugar-induced signals regulate sweet and fat taste perception in Drosophila.

In this study, we investigate the interplay between taste perception and macronutrients. While sugar's and protein's self-regulation of taste perception is known, the role of fat remains unclear. We reveal that in Drosophila, fat overconsumption reduces fatty acid taste in favor of sweet perception. Conversely, sugar intake increases fatty acid perception and suppresses sweet taste. Genetic investigations show that the sugar signal, gut-secreted Hedgehog, suppresses sugar taste and enhances fatty acid perception. Fat overconsumption induces unpaired 2 (Upd2) secretion from adipose tissue to the hemolymph. We reveal taste neurons take up Upd2, which triggers Domeless suppression of fatty acid perception. We further show that the downstream JAK/STAT signaling enhances sweet perception and, via Socs36E, fine-tunes Domeless activity and the fatty acid taste perception. Together, our results show that sugar regulates Hedgehog signaling and fat induces Upd2 signaling to balance nutrient intake and to regulate sweet and fat taste perception.

Hedgehog-mediated gut-taste neuron axis controls sweet perception in Drosophila.

Dietary composition affects food preference in animals. High sugar intake suppresses sweet sensation from insects to humans, but the molecular basis of this suppression is largely unknown. Here, we reveal that sugar intake in Drosophila induces the gut to express and secrete Hedgehog (Hh) into the circulation. We show that the midgut secreted Hh localize to taste sensilla and suppresses sweet sensation, perception, and preference. We further find that the midgut Hh inhibits Hh signalling in the sweet taste neurons. Our electrophysiology studies demonstrate that the midgut Hh signal also suppresses bitter taste and some odour responses, affecting overall food perception and preference. We further show that the level of sugar intake during a critical window early in life, sets the adult gut Hh expression and sugar perception. Our results together reveal a bottom-up feedback mechanism involving a "gut-taste neuron axis" that regulates food sensation and preference.

Semi-Supervised Learning for Forklift Activity Recognition from Controller Area Network (CAN) Signals.

Machine Activity Recognition (MAR) can be used to monitor manufacturing processes and find bottlenecks and potential for improvement in production. Several interesting results on MAR techniques have been produced in the last decade, but mostly on construction equipment. Forklift trucks, which are ubiquitous and highly important industrial machines, have been missing from the MAR research. This paper presents a data-driven method for forklift activity recognition that uses Controller Area Network (CAN) signals and semi-supervised learning (SSL). The SSL enables the utilization of large quantities of unlabeled operation data to build better classifiers; after a two-step post-processing, the recognition results achieve balanced accuracy of 88% for driving activities and 95% for load-handling activities on a hold-out data set. In terms of the Matthews correlation coefficient for five activity classes, the final score is 0.82, which is equal to the recognition results of two non-domain experts who use videos of the activities. A particular success is that context can be used to capture the transport of small weight loads that are not detected by the forklift's built-in weight sensor.

The intraparietal sulcus governs multisensory integration of audiovisual information based on task difficulty.

Object recognition benefits maximally from multimodal sensory input when stimulus presentation is noisy, or degraded. Whether this advantage can be attributed specifically to the extent of overlap in object-related information, or rather, to object-unspecific enhancement due to the mere presence of additional sensory stimulation, remains unclear. Further, the cortical processing differences driving increased multisensory integration (MSI) for degraded compared with clear information remain poorly understood. Here, two consecutive studies first compared behavioral benefits of audio-visual overlap of object-related information, relative to conditions where one channel carried information and the other carried noise. A hierarchical drift diffusion model indicated performance enhancement when auditory and visual object-related information was simultaneously present for degraded stimuli. A subsequent fMRI study revealed visual dominance on a behavioral and neural level for clear stimuli, while degraded stimulus processing was mainly characterized by activation of a frontoparietal multisensory network, including IPS. Connectivity analyses indicated that integration of degraded object-related information relied on IPS input, whereas clear stimuli were integrated through direct information exchange between visual and auditory sensory cortices. These results indicate that the inverse effectiveness observed for identification of degraded relative to clear objects in behavior and brain activation might be facilitated by selective recruitment of an executive cortical network which uses IPS as a relay mediating crossmodal sensory information exchange.

A mammalian blood odor component serves as an approach-avoidance cue across phylum border - from flies to humans.

Chemosignals are used by predators to localize prey and by prey to avoid predators. These cues vary between species, but the odor of blood seems to be an exception and suggests the presence of an evolutionarily conserved chemosensory cue within the blood odor mixture. A blood odor component, E2D, has been shown to trigger approach responses identical to those triggered by the full blood odor in mammalian carnivores and as such, is a key candidate as a food/alarm cue in blood. Using a multidisciplinary approach, we demonstrate that E2D holds the dual function of affecting both approach and avoidance behavior in a predator-prey predicted manner. E2D evokes approach responses in two taxonomically distant blood-seeking predators, Stable fly and Wolf, while evoking avoidance responses in the prey species Mouse. We extend this by demonstrating that this chemical cue is preserved in humans as well; E2D induces postural avoidance, increases physiological arousal, and enhances visual perception of affective stimuli. This is the first demonstration of a single chemical cue with the dual function of guiding both approach and avoidance in a predator-prey predicted manner across taxonomically distant species, as well as the first known chemosignal that affects both human and non-human animals alike.

Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation.

Task-based fMRI has been used to study the effects of experimental inflammation on the human brain, but it remains unknown whether intrinsic connectivity in the brain at rest changes during a sickness response. Here, we investigated the effect of experimental inflammation on connectivity between areas relevant for monitoring of bodily states, motivation, and subjective symptoms of sickness. In a double-blind randomized controlled experiment, 52 healthy volunteers were injected with 0.6ng/kg LPS (lipopolysaccharide) or placebo, and participated in a resting state fMRI experiment after approximately 2h 45min. Resting state fMRI data were available from 48 participants, of which 28 received LPS and 20 received placebo. Bilateral anterior and bilateral posterior insula sections were used as seed regions and connectivity with bilateral orbitofrontal and cingulate (anterior and middle) cortices was investigated. Back pain, headache and global sickness increased significantly after as compared to before LPS, while a non-significant trend was shown for increased nausea. Compared to placebo, LPS was followed by increased connectivity between left anterior insula and left midcingulate cortex. This connectivity was significantly correlated to increase in back pain after LPS and tended to be related to increased global sickness, but was not related to increased headache or nausea. LPS did not affect the connectivity from other insular seeds. In conclusion, the finding of increased functional connectivity between left anterior insula and middle cingulate cortex suggests a potential neurophysiological mechanism that can be further tested to understand the subjective feeling of malaise and discomfort during a sickness response.

Bayesian-based integration of multisensory naturalistic perithreshold stimuli.

Most studies exploring multisensory integration have used clearly perceivable stimuli. According to the principle of inverse effectiveness, the added neural and behavioral benefit of integrating clear stimuli is reduced in comparison to stimuli with degraded and less salient unisensory information. Traditionally, speed and accuracy measures have been analyzed separately with few studies merging these to gain an understanding of speed-accuracy trade-offs in multisensory integration. In two separate experiments, we assessed multisensory integration of naturalistic audio-visual objects consisting of individually-tailored perithreshold dynamic visual and auditory stimuli, presented within a multiple-choice task, using a Bayesian Hierarchical Drift Diffusion Model that combines response time and accuracy. For both experiments, unisensory stimuli were degraded to reach a 75% identification accuracy level for all individuals and stimuli to promote multisensory binding. In Experiment 1, we subsequently presented uni- and their respective bimodal stimuli followed by a 5-alternative-forced-choice task. In Experiment 2, we controlled for low-level integration and attentional differences. Both experiments demonstrated significant superadditive multisensory integration of bimodal perithreshold dynamic information. We present evidence that the use of degraded sensory stimuli may provide a link between previous findings of inverse effectiveness on a single neuron level and overt behavior. We further suggest that a combined measure of accuracy and reaction time may be a more valid and holistic approach of studying multisensory integration and propose the application of drift diffusion models for studying behavioral correlates as well as brain-behavior relationships of multisensory integration.

Sexual orientation related differences in cortical thickness in male individuals.

Previous neuroimaging studies demonstrated sex and also sexual orientation related structural and functional differences in the human brain. Genetic information and effects of sex hormones are assumed to contribute to the male/female differentiation of the brain, and similar effects could play a role in processes influencing human's sexual orientation. However, questions about the origin and development of a person's sexual orientation remain unanswered, and research on sexual orientation related neurobiological characteristics is still very limited. To contribute to a better understanding of the neurobiology of sexual orientation, we used magnetic resonance imaging (MRI) in order to compare regional cortical thickness (Cth) and subcortical volumes of homosexual men (hoM), heterosexual men (heM) and heterosexual women (heW). hoM (and heW) had thinner cortices primarily in visual areas and smaller thalamus volumes than heM, in which hoM and heW did not differ. Our results support previous studies, which suggest cerebral differences between hoM and heM in regions, where sex differences have been reported, which are frequently proposed to underlie biological mechanisms. Thus, our results contribute to a better understanding of the neurobiology of sexual orientation.

The influence of work-related chronic stress on the regulation of emotion and on functional connectivity in the brain.

Despite mounting reports about the negative effects of chronic occupational stress on cognitive and emotional functions, the underlying mechanisms are unknown. Recent findings from structural MRI raise the question whether this condition could be associated with a functional uncoupling of the limbic networks and an impaired modulation of emotional stress. To address this, 40 subjects suffering from burnout symptoms attributed to chronic occupational stress and 70 controls were investigated using resting state functional MRI. The participants' ability to up- regulate, down-regulate, and maintain emotion was evaluated by recording their acoustic startle response while viewing neutral and negatively loaded images. Functional connectivity was calculated from amygdala seed regions, using explorative linear correlation analysis. Stressed subjects were less capable of down-regulating negative emotion, but had normal acoustic startle responses when asked to up-regulate or maintain emotion and when no regulation was required. The functional connectivity between the amygdala and the anterior cingulate cortex correlated with the ability to down-regulate negative emotion. This connectivity was significantly weaker in the burnout group, as was the amygdala connectivity with the dorsolateral prefrontal cortex and the motor cortex, whereas connectivity from the amygdala to the cerebellum and the insular cortex were stronger. In subjects suffering from chronic occupational stress, the functional couplings within the emotion- and stress-processing limbic networks seem to be altered, and associated with a reduced ability to down-regulate the response to emotional stress, providing a biological substrate for a further facilitation of the stress condition.