Characterization of the synaptic properties of olfactory bulb projections

The olfactory bulb directly projects to several diverse telencephalic structures, but, to date, few studies have investigated the physiological characteristics of most of these areas. As an initial step towards understanding the odor processing functions of these secondary olfactory structures, we recorded evoked field potentials in response to lateral olfactory tract stimulation in vivo in urethane-anesthetized Sprague-Dawley rats in the following brain structures: anterior olfactory nucleus, ventral and dorsal tenia tecta, olfactory tubercle, anterior and posterior piriform cortex, the anterior cortical nucleus of the amygdala, and lateral entorhinal cortex. Using paired-pulse stimulation with interpulse intervals of 25-1000 ms, we observed facilitation of the response to the second pulse in every structure examined, although the degree of facilitation varied among the target structures. Additionally, pulse train stimulation at three different frequencies (40, 10 and 2 Hz) produced facilitation of evoked field potentials that also varied among target structures. We discuss the potential utility of such short-term facilitation in olfactory processing.     

Changes in Cerebral Blood Flow during Olfactory Stimulation in Patients with Multiple Chemical Sensitivity: A Multi-Channel Near-Infrared Spectroscopic Study

Multiple chemical sensitivity (MCS) is characterized by somatic distress upon exposure to odors. Patients with MCS process odors differently from controls. This odor-processing may be associated with activation in the prefrontal area connecting to the anterior cingulate cortex, which has been suggested as an area of odorant-related activation in MCS patients. In this study, activation was defined as a significant increase in regional cerebral blood flow (rCBF) because of odorant stimulation. Using the well-designed card-type olfactory test kit, changes in rCBF in the prefrontal cortex (PFC) were investigated after olfactory stimulation with several different odorants. Near-infrared spectroscopic (NIRS) imaging was performed in 12 MCS patients and 11 controls. The olfactory stimulation test was continuously repeated 10 times. The study also included subjective assessment of physical and psychological status and the perception of irritating and hedonic odors. Significant changes in rCBF were observed in the PFC of MCS patients on both the right and left sides, as distinct from the center of the PFC, compared with controls. MCS patients adequately distinguished the non-odorant in 10 odor repetitions during the early stage of the olfactory stimulation test, but not in the late stage. In comparison to controls, autonomic perception and negative affectivity were poorer in MCS patients. These results suggest that prefrontal information processing associated with odor-processing neuronal circuits and memory and cognition processes from past experience of chemical exposure play significant roles in the pathology of this disorder.     

Dissociated representations of pleasant and unpleasant olfacto-trigeminal mixtures: an FMRI study

How the pleasantness of chemosensory stimuli such as odorants or intranasal trigeminal compounds is processed in the human brain has been the focus of considerable recent interest. Yet, so far, only the unimodal form of this hedonic processing has been explored, and not its bimodal form during crossmodal integration of olfactory and trigeminal stimuli. The main purpose of the present study was to investigate this question. To this end, functional magnetic resonance imaging (fMRI) was used in an experiment comparing brain activation related to a pleasant and a relatively unpleasant olfacto-trigeminal mixture, and to their individual components (CO(2) alone, Orange alone, Rose alone). Results revealed first common neural activity patterns in response to both mixtures in a number of regions: notably the superior temporal gyrus and the caudate nucleus. Common activations were also observed in the insula, although the pleasant mixture activated the right insula whereas the unpleasant mixture activated the left insula. However, specific activations were observed in anterior cingulate gyrus and the ventral tegmental area only during the perception of the pleasant mixture. These findings emphasized for the firs time the involvement of the latter structures in processing of pleasantness during crossmodal integration of chemosensory stimuli.     

Why do capuchin monkeys urine wash? An experimental test of the sexual communication hypothesis using fMRI

Urine washing (UW) consists of depositing urine on the hands and vigorously rubbing the body. As urine contains chemical and pheromonal cues, UW may convey socially relevant information. Although ritualized UW is observed in many New World primates, including capuchin monkeys, the functional significance of UW remains unclear. In this experiment, we investigated the social signaling hypothesis of UW. Specifically, we hypothesized that UW by males conveys socially relevant signals that females can detect. We used functional magnetic resonance imaging (fMRI) to test whether adult female capuchins show differential brain activation in response to adult male and juvenile male capuchin urine. We expected to see changes in activation of structures involved in olfactory processing, including the piriform cortex, medial preoptic and anterior hypothesis, orbitofrontal cortex, hippocampus, and cerebellum. Data were acquired from four adult female capuchin monkeys. Presentations of odor stimuli (obtained from unfamiliar males) were made during fMRI acquisition using a standard ON-OFF design. All fMRI data were spatially normalized to a template and analyzed using the FMRI Expert Analysis Tool Version 5.98, part of the FMRIB's Software Library (www.fmrib.ox.ac.uk/fsl). Whole brain analyses revealed significant activations in the inferior temporal cortex, parahippocampal gyrus, precuneus, hippocampus, pulvinar, and cerebellum when females were presented with the adult male urine. Notably, significantly greater signal activation was observed in several regions associated with olfactory processing, when subjects were presented with adult male urine as compared with urine from juvenile males. Our results indicate that UW serves a social communicative function in capuchins, providing support for the sexual signaling hypothesis.     

Evidence for central command activation of the human insular cortex during exercise.

The purpose of this investigation was to determine whether central command activated regions of the insular cortex, independent of muscle metaboreflex activation and blood pressure elevations. Subjects (n = 8) were studied during 1) rest with cuff occlusion, 2) static handgrip exercise (SHG) sufficient to increase mean blood pressure (MBP) by 15 mmHg, and 3) post-SHG exercise cuff occlusion (PECO) to sustain the 15-mmHg blood pressure increase. Data were collected for heart rate, MBP, ratings of perceived exertion and discomfort, and regional cerebral blood flow (rCBF) by using single-photon-emission computed tomography. When time periods were compared when MBP was matched during SHG and PECO, heart rate (7 +/- 3 beats/min; P < 0.05) and ratings of perceived exertion (15 +/- 2 units; P < 0.05) were higher for SHG. During SHG, there were significant increases in rCBF for hand sensorimotor (9 +/- 3%), right inferior posterior insula (7 +/- 3%), left inferior anterior insula (8 +/- 2%), and anterior cingluate regions (6 +/- 2%), not found during PECO. There was significant activation of the inferior (ventral) thalamus and right inferior anterior insular for both SHG and PECO. Although prior studies have shown that regions of the insular cortex can be activated independent of mechanoreflex input, it was not presently assessed. These findings provide evidence that there are rCBF changes within regions of the insular and anterior cingulate cortexes related to central command per se during handgrip exercise, independent of metaboreflex activation and blood pressure elevation.     

The influence of training on chemosensory event-related potentials and interactions between the olfactory and trigeminal systems

It is not possible to accurately predict the perceptual response to odorants and odorant mixtures without understanding patterns of suppression and facilitation that result from interactions between the olfactory and trigeminal systems. The current study extends previous findings by exploring the effect of intensive training on the interaction between these systems and also by using a different mixed chemosensory stimulus to examine whether the principles established in earlier studies generalize to different odorants. Stimuli were chosen so as to selectively activate the olfactory (H2S) and trigeminal (CO2) nerves. In addition, linalool was included as a stimulus that activated both systems. Thirty-five participants (19 men, 16 women) rated the intensity of each stimulus when presented both alone and in binary mixtures (linalool + H2S, and linalool + CO2). Chemosensory event-related potentials were obtained from three recording positions. Analysis of intensity ratings showed that linalool was significantly less intense than the other stimuli when presented alone. In binary mixtures, H2S was strongly suppressed by linalool. One week of intensive odor training produced significant and specific reductions in the intensity of linalool and H2S, both alone and in their mixture. Training with a different odor (champignol) had no effect. Chemosensory event-related potential data confirmed previous findings showing changes in topographical distribution that reflected the degree of trigeminal activity. Binary mixtures generally produced larger amplitudes than single stimuli. Latencies clearly differentiated between the three single stimuli and the binary mixtures. Changes were observed in event-related potentials that reflected those obtained for intensity ratings in that they were observed for linalool and H2S in the linalool trained group only. The amplitude of the late 'endogenous' component (P3) was significantly decreased for these odors at frontal recording sites. In summary, strong and specific training effects were observed in intensity ratings for participants trained with the test odor (linalool), but not for those trained with a different odor. This was supported by a significant decrease of amplitudes of the event-related potentials at frontal recording sites following training with the test odor only     

Neural activation in women in response to masculinized male faces: mediation by hormones and psychosexual factors

Women's preference for masculine faces varies with hormonal state, sociosexuality, and relationship status, but the underlying mechanisms are poorly understood. We hypothesized that hormones and psychosexual factors (sociosexuality, sexual inhibition/excitation) mediate the perception and evaluation of male faces thereby influencing women's preferences. We used functional magnetic resonance imaging to measure brain activity in 12 women as they evaluated pictures of male faces (half 30% masculinized, half 30% feminized). Participants were heterosexual women, age 23–28 years, who were not in a committed relationship and not using hormonal contraception. Women were tested during both the follicular and luteal phase of their menstrual cycle. We found five brain regions related to face and risk processing that responded more to the masculinized than to the feminized faces, including the superior temporal gyrus, precentral gyrus, posterior cingulate cortex, inferior parietal lobule, and anterior cingulate cortex. Increased activation in the anterior cingulate cortex, specifically, may indicate that women perceive masculinized faces to be both more risky and more attractive. We did not see any areas that were more strongly activated by feminized faces. Levels of activation were influenced by hormonal and psychosexual factors. The patterns of hormonally and psychosexually mediated neural activation observed may offer insight into the cognitive processes underlying women's partner preferences.     

Spared Piriform Cortical Single-Unit Odor Processing and Odor Discrimination in the Tg2576 Mouse Model of Alzheimer's Disease

Alzheimer''s disease is a neurodegenerative disorder that is the most common cause of dementia in the elderly today. One of the earliest reported signs of Alzheimer''s disease is olfactory dysfunction, which may manifest in a variety of ways. The present study sought to address this issue by investigating odor coding in the anterior piriform cortex, the primary cortical region involved in higher order olfactory function, and how it relates to performance on olfactory behavioral tasks. An olfactory habituation task was performed on cohorts of transgenic and age-matched wild-type mice at 3, 6 and 12 months of age. These animals were then anesthetized and acute, single-unit electrophysiology was performed in the anterior piriform cortex. In addition, in a separate group of animals, a longitudinal odor discrimination task was conducted from 3–12 months of age. Results showed that while odor habituation was impaired at all ages, Tg2576 performed comparably to age-matched wild-type mice on the olfactory discrimination task. The behavioral data mirrored intact anterior piriform cortex single-unit odor responses and receptive fields in Tg2576, which were comparable to wild-type at all age groups. The present results suggest that odor processing in the olfactory cortex and basic odor discrimination is especially robust in the face of amyloid β precursor protein (AβPP) over-expression and advancing amyloid β (Aβ) pathology. Odor identification deficits known to emerge early in Alzheimer''s disease progression, therefore, may reflect impairments in linking the odor percept to associated labels in cortical regions upstream of the primary olfactory pathway, rather than in the basic odor processing itself.     

Letter to the Editor: Seasonal Pattern of Births in Patients with Optic Neuritis

Attentional processes are fundamental to good cognitive functioning of human operators. The purpose of this study was to analyze the activity of neuronal networks involved in the orienting attention and executive control processes from the perspective of diurnal variability. Twenty-three healthy male volunteers meeting magnetic resonance (MR) inclusion criteria performed the Stroop Color-Word task (block design) in the MR scanner five times/day (06:00, 10:00, 14:00, 18:00, 22:00 h). The first scanning session was scheduled 1–1.5 h after waking. Between MR sessions, subjects performed simulated driving tasks in stable environmental conditions, with controlled physical activity and diet. Significant activation was found in brain regions related to the orienting attentional system: the parietal lobe (BA40) and frontal eye-fields (FEFs). There were also activations in areas of the executive control system: the fronto-insular cortex (FIC), dorsal anterior cingulate cortex (dACC), presupplementary motor area (preSMA), supplementary motor area (SMA), basal ganglia, middle temporal (MT; BA21), and dorsolateral prefrontal cortex (DLPFC), as a part of the central executive network. Significant deactivations were observed in the rostral anterior cingulate cortex (rACC), posterior cingulate cortex (PCC), superior frontal gyrus (SF), parietal lobe (BA39), and parahippocampal that are thought to comprise the default mode network (DMN). Additionally, the activated regions included bilaterally lingual gyrus and fusiform gyrus. The insula was bilaterally deactivated. Visual attention controlled by the goal-oriented attention system and comprising top-down and bottom-up mechanisms, activated by Stroop-like task, turned out to be prone to diurnal changes. The study results show the occurrence of time-of-day–related variations in neural activity of brain regions linked to the orienting attentional system (left parietal lobe—BA40, left and right FEFs), simultaneously providing arguments for temporal stability of the executive system and default mode network. These results also seem to suggest that the involuntary, exogenous (bottom-up) mechanism of attention is more vulnerable to circadian and fatigue factors than the voluntary (top-down) mechanism, which appear to be maintained at the same functional level during the day. The above phenomena were observed at the neural level. (Author correspondence: marek@uj.edu.pl)     

Changes in regional cerebral blood flow distribution during postexercise hypotension in humans.

This investigation compared patterns of regional cerebral blood flow (rCBF) during exercise recovery both with and without postexercise hypotension (PEH). Eight subjects were studied on 3 days with randomly assigned conditions: 1) after 30 min of rest; 2) after 30 min of moderate exercise (M-Ex) at 60-70% heart rate (HR) reserve during PEH; and 3) after 30 min of light exercise (L-Ex) at 20% HR reserve with no PEH. Data were collected for HR, mean blood pressure (MBP), and ratings of perceived exertion and relaxation, and rCBF was assessed by use of single-photon-emission computed tomography. With the use of ANOVA across conditions, there were differences (P < 0.05; mean +/- SD) from rest during exercise recovery from M-Ex (HR = +12 +/- 3 beats/min; MBP = -9 +/- 2 mmHg), but not from L-Ex (HR = +2 +/- 2 beats/min; MBP = -2 +/- 2 mmHg). After M-Ex, there were decreases (P < 0.05) for the anterior cingulate (-6.7 +/- 2%), right and left inferior thalamus (-10 +/- 3%), right inferior insula (-13 +/- 3%), and left inferior anterior insula (-8 +/- 3%), not observed after L-Ex. There were rCBF decreases for leg sensorimotor regions after both M-Ex (-15 +/- 4%) and L-Ex (-12 +/- 3%) and for the left superior anterior insula (-7 +/- 3% and -6 +/- 3%), respectively. Data show that there are rCBF reductions within specific regions of the insular cortex and anterior cingulate cortex coupled with a postexercise hypotensive response after M-Ex. Findings suggest that these cerebral cortical regions, previously implicated in cardiovascular regulation during exercise, may also be involved in PEH.     

The Neural Basis of Testable and Non-Testable Beliefs

Beliefs about the state of the world are an important influence on both normal behavior and psychopathology. However, understanding of the neural basis of belief processing remains incomplete, and several aspects of belief processing have only recently been explored. Specifically, different types of beliefs may involve fundamentally different inferential processes and thus recruit distinct brain regions. Additionally, neural processing of truth and falsity may differ from processing of certainty and uncertainty. The purpose of this study was to investigate the neural underpinnings of assessment of testable and non-testable propositions in terms of truth or falsity and the level of certainty in a belief. Functional magnetic resonance imaging (fMRI) was used to study 14 adults while they rated propositions as true or false and also rated the level of certainty in their judgments. Each proposition was classified as testable or non-testable. Testable propositions activated the DLPFC and posterior cingulate cortex, while non-testable statements activated areas including inferior frontal gyrus, superior temporal gyrus, and an anterior region of the superior frontal gyrus. No areas were more active when a proposition was accepted, while the dorsal anterior cingulate was activated when a proposition was rejected. Regardless of whether a proposition was testable or not, certainty that the proposition was true or false activated a common network of regions including the medial prefrontal cortex, caudate, posterior cingulate, and a region of middle temporal gyrus near the temporo-parietal junction. Certainty in the truth or falsity of a non-testable proposition (a strong belief without empirical evidence) activated the insula. The results suggest that different brain regions contribute to the assessment of propositions based on the type of content, while a common network may mediate the influence of beliefs on motivation and behavior based on the level of certainty in the belief.     

Mirroring Pain in the Brain: Emotional Expression versus Motor Imitation

Perception of pain in others via facial expressions has been shown to involve brain areas responsive to self-pain, biological motion, as well as both performed and observed motor actions. Here, we investigated the involvement of these different regions during emotional and motor mirroring of pain expressions using a two-task paradigm, and including both observation and execution of the expressions. BOLD responses were measured as subjects watched video clips showing different intensities of pain expression and, after a variable delay, either expressed the amount of pain they perceived in the clips (pain task), or imitated the facial movements (movement task). In the pain task condition, pain coding involved overlapping activation across observation and execution in the anterior cingulate cortex, supplementary motor area, inferior frontal gyrus/anterior insula, and the inferior parietal lobule, and a pain-related increase (pain vs. neutral) in the anterior cingulate cortex/supplementary motor area, the right inferior frontal gyrus, and the postcentral gyrus. The ‘mirroring’ response was stronger in the inferior frontal gyrus and middle temporal gyrus/superior temporal sulcus during the pain task, and stronger in the inferior parietal lobule in the movement task. These results strongly suggest that while motor mirroring may contribute to the perception of pain expressions in others, interpreting these expressions in terms of pain content draws more heavily on networks involved in the perception of affective meaning.     

Odor similarity does not influence the time needed for odor processing

The brain's link between perception and action involves several steps, which include stimulus transduction, neuronal coding of the stimulus, comparison to a memory template and choice of an appropriate behavioral response. All of these need time, and many studies report that the time needed to compare two stimuli correlates inversely with the perceived distance between them. We developed a behavioral assay in which we tested the time that a honeybee needs to discriminate between odors consisting of mixtures of two components, and included both very similar and very different stimuli spanning four log-concentration ranges. Bees learned to discriminate all odors, including very similar odors and the same odor at different concentrations. Even though discriminating two very similar odors appears to be a more difficult task than discriminating two very distinct substances, we found that the time needed to make a choice for or against an odor was independent of odor similarity. Our data suggest that, irrespective of the nature of the olfactory code, the bee olfactory system evaluates odor quality after a constant interval. This may ensure that odors are only assessed after the olfactory network has optimized its representation.     

Androstenol – a Steroid Derived Odor Activates the Hypothalamus in Women

Background

Whether pheromone signaling exists in humans is still a matter of intense discussion. In the present study we tested if smelling of Androstenol, a steroid produced by the human body and reported to affect human behavior, may elicit cerebral activation. A further issue was to evaluate whether the pattern of activation resembles the pattern of common odors.

Methodology

PET measurements of regional cerebral blood flow (rCBF) were conducted in 16 healthy heterosexual women during passive smelling of Androstenol, four ordinary odors (OO), and odorless air (the base line condition).

Principal findings

Smelling Androstenol caused activation of a portion of the hypothalamus, which according to animal data mediates the pheromone triggered mating behavior. Smelling of OO, on the other hand, engaged only the classical olfactory regions (the piriform cortex, lateral amygdala, anterior insular and anterior cingulate cortex).

Conclusions

The observed pattern of activation is very similar to the pattern previously detected with 4,16-androstadien-3-one in heterosexual females. It suggests that several compounds released by human body may activate cerebral networks involved in human reproduction.     

Dissociable codes of odor quality and odorant structure in human piriform cortex

The relationship between odorant structure and odor quality has been a focus of olfactory research for 100 years, although no systematic correlations are yet apparent. Animal studies suggest that topographical representations of odorant structure in olfactory bulb form the perceptual basis of odor quality. Whether central olfactory regions are similarly organized is unclear. Using an olfactory version of fMRI cross-adaptation, we measured neural responses in primary olfactory (piriform) cortex as subjects smelled pairs of odorants systematically differing in quality and molecular functional group (as one critical attribute of odorant structure). Our results indicate a double dissociation in piriform cortex, whereby posterior regions encode quality (but not structure) and anterior regions encode structure (but not quality). The presence of structure-based codes suggests fidelity of sensory information arising from olfactory bulb. In turn, quality-based codes are independent of any simple structural configuration, implying that synthetic mechanisms may underlie our experience of smell.     

Odor representations in olfactory cortex: distributed rate coding and decorrelated population activity

How information encoded in neuronal spike trains is used to guide sensory decisions is a fundamental question. In olfaction, a single sniff is sufficient for fine odor discrimination but the neural representations on which olfactory decisions are based are unclear. Here, we recorded neural ensemble activity in the anterior piriform cortex (aPC) of rats performing an odor mixture categorization task. We show that odors evoke transient bursts locked to sniff onset and that odor identity can be better decoded using burst spike counts than by spike latencies or temporal patterns. Surprisingly, aPC ensembles also exhibited near-zero noise correlations during odor stimulation. Consequently, fewer than 100 aPC neurons provided sufficient information to account for behavioral speed and accuracy, suggesting that behavioral performance limits arise downstream of aPC. These findings demonstrate profound transformations in the dynamics of odor representations from the olfactory bulb to cortex and reveal likely substrates for odor-guided decisions. VIDEO ABSTRACT:     

Altered odor-induced expression of c-fos and arg 3.1 immediate early genes in the olfactory system after familiarization with an odor

In adult rats, repeated exposure to an odorant, in absence of any experimentally delivered reinforcement, leads to a drastic decrease in mitral/tufted (M/T) cell responsiveness, not only for the familiar odor but also for other novel odors. In the present study, using two different and complementary in situ hybridization methods, we analyzed the effect of familiarization with an odorant on c-fos and arg 3.1 mRNA expression levels, and we examined the odor specificity of this effect. Odor exposure induces a specific increase in c-fos and arg 3.1 expression in some particular olfactory bulb quadrants. Previous familiarization with the test odor results in a decreased expression of both IEGs in these quadrants, leading to the alteration of the odor-specific pattern of c-fos and arg 3.1 expression. In contrast, this odor-specific pattern is not affected when different odors are used for familiarization and test. Similarly, an odor-specific familiarization effect leading to a reduced c-fos and arg 3.1 expression was also detected in the cingulate cortex and in the anterior piriform cortex. These results support our hypothesis that the decrease in M/T cell responsiveness following a preceding familiarization with an odorant may be related to a particular form of synaptic plasticity involving changes at the genomic level, and reveals further insight in olfactory information processing and the cellular mechanisms underlying familiarization in the olfactory system.     

Olfactory metacognition

The current paper focuses on the subjective knowledge people have about their ability to name odors. Previous investigations of such metacognitive aspects of olfactory cognition are very scarce and have yielded results that need further scrutiny. In two experiments, we investigated three metamemory judgments about odor identity. As opposed to previous findings, participants' feeling of knowing judgments about odor identity predicted later recognition. Participants were also accurate but highly overconfident in their retrospective confidence in odor identification. A strong and imminent feeling of being able to name an odor, a so-called 'tip of the nose' experience, was found to predict later recall, but was otherwise poorly related to any partial activation of the odor name or other information associated with the odor. This makes it different from the commonly investigated 'tip of the tongue' phenomenon. The current study shows that olfactory metamemory is related to actual knowledge, a finding that is in line with what has been observed for other modalities.     

Olfactory functions are mediated by parallel and hierarchical processing

How the human brain processes the perception, discrimination, and recognition of odors has not been systematically explored. Cerebral activations were therefore studied with PET during five different olfactory tasks: monorhinal smelling of odorless air (AS), single odors (OS), discrimination of odor intensity (OD-i), discrimination of odor quality (OD-q), and odor recognition memory (OM). OS activated amygdala-piriform, orbitofrontal, insular, and cingulate cortices and right thalamus. OD-i and OD-q both engaged left insula and right cerebellum. OD-q also involved other areas, including right caudate and subiculum. OM did not activate the insula, but instead, the piriform cortex. With the exception of caudate and subiculum, it shared the remaining activations with the OD-q, and engaged, in addition, the temporal and parietal cortices. These findings indicate that olfactory functions are organized in a parallel and hierarchical manner.