De Novo Emergence of Odor Category Representations in the Human Brain.

Categorization allows organisms to efficiently extract relevant information from a diverse environment. Because of the multidimensional nature of odor space, this ability is particularly important for the olfactory system. However, categorization relies on experience, and the processes by which the human brain forms categorical representations about new odor percepts are currently unclear. Here we used olfactory psychophysics and multivariate fMRI techniques, in the context of a paired-associates learning task, to examine the emergence of novel odor category representations in the human brain. We found that learning between novel odors and visual category information induces a perceptual reorganization of those odors, in parallel with the emergence of odor category-specific ensemble patterns in perirhinal, orbitofrontal, piriform, and insular cortices. Critically, the learning-induced pattern effects in orbitofrontal and perirhinal cortex predicted the magnitude of categorical learning and perceptual plasticity. The formation of de novo category-specific representations in olfactory and limbic brain regions suggests that such ensemble patterns subserve the development of perceptual classes of information, and imply that these patterns are instrumental to the brain's capacity for odor categorization. SIGNIFICANCE STATEMENT: How the human brain assigns novel odors to perceptual classes and categories is poorly understood. We combined an olfactory-visual paired-associates task with multivariate pattern-based fMRI approaches to investigate the de novo formation of odor category representations within the human brain. The identification of emergent odor category codes within the perirhinal, piriform, orbitofrontal, and insular cortices suggests that these regions can integrate multimodal sensory input to shape category-specific olfactory representations for novel odors, and may ultimately play an important role in assembling each individual's semantic knowledge base of the olfactory world.

Layer-Specific fMRI Responses to Excitatory and Inhibitory Neuronal Activities in the Olfactory Bulb.

High-resolution functional magnetic resonance imaging (fMRI) detects localized neuronal activity via the hemodynamic response, but it is unclear whether it accurately identifies neuronal activity specific to individual layers. To address this issue, we preferentially evoked neuronal activity in superficial, middle, and deep layers of the rat olfactory bulb: the glomerular layer by odor (5% amyl acetate), the external plexiform layer by electrical stimulation of the lateral olfactory tract (LOT), and the granule cell layer by electrical stimulation of the anterior commissure (AC), respectively. Electrophysiology, laser-Doppler flowmetry of cerebral blood flow (CBF), and blood oxygenation level-dependent (BOLD) and cerebral blood volume-weighted (CBV) fMRI at 9.4 T were performed independently. We found that excitation of inhibitory granule cells by stimulating LOT and AC decreased the spontaneous multi-unit activities of excitatory mitral cells and subsequently increased CBF, CBV, and BOLD signals. Odor stimulation also increased the hemodynamic responses. Furthermore, the greatest CBV fMRI responses were discretely separated into the same layers as the evoked neuronal activities for all three stimuli, whereas BOLD was poorly localized with some exception to the poststimulus undershoot. In addition, the temporal dynamics of the fMRI responses varied depending on the stimulation pathway, even within the same layer. These results indicate that the vasculature is regulated within individual layers and CBV fMRI has a higher fidelity to the evoked neuronal activity compared with BOLD. Our findings are significant for understanding the neuronal origin and spatial specificity of hemodynamic responses, especially for the interpretation of laminar-resolution fMRI. SIGNIFICANCE STATEMENT: Functional magnetic resonance imaging (fMRI) is a noninvasive, in vivo technique widely used to map function of the entire brain, including deep structures, in animals and humans. However, it measures neuronal activity indirectly by way of the vascular response. It is currently unclear how finely the hemodynamic response is regulated within single cortical layers and whether increased inhibitory neuronal activities affect fMRI signal changes. Both laminar specificity and the neural origins of fMRI are important to interpret functional maps properly, which we investigated by activating discrete rat olfactory bulb circuits.

Networks involved in olfaction and their dynamics using independent component analysis and unified structural equation modeling.

The study of human olfaction is complicated by the myriad of processing demands in conscious perceptual and emotional experiences of odors. Combining functional magnetic resonance imaging with convergent multivariate network analyses, we examined the spatiotemporal behavior of olfactory-generated blood-oxygenated-level-dependent signal in healthy adults. The experimental functional magnetic resonance imaging (fMRI) paradigm was found to offset the limitations of olfactory habituation effects and permitted the identification of five functional networks. Analysis delineated separable neuronal circuits that were spatially centered in the primary olfactory cortex, striatum, dorsolateral prefrontal cortex, rostral prefrontal cortex/anterior cingulate, and parietal-occipital junction. We hypothesize that these functional networks subserve primary perceptual, affective/motivational, and higher order olfactory-related cognitive processes. Results provided direct evidence for the existence of parallel networks with top-down modulation for olfactory processing and clearly distinguished brain activations that were sniffing-related versus odor-related. A comprehensive neurocognitive model for olfaction is presented that may be applied to broader translational studies of olfactory function, aging, and neurological disease.

Resolution of diminished olfactory sensation after treatment of bilateral ophthalmic segment aneurysms with flow diversion: case report.

BACKGROUND AND IMPORTANCE: Olfactory tract dysfunction due to an unruptured intracranial aneurysm is rare. We present a case in which a patient with impaired olfaction related to bilateral internal carotid artery aneurysms experienced subjective and quantitative objective improvement of olfactory sensation after treatment of ophthalmic segment aneurysms with flow diversion. CLINICAL PRESENTATION: A 44-year-old woman presented with hyposmia and bilateral ophthalmic segment internal carotid artery aneurysms. The symptom of hyposmia, worsening over a period of several months, was suspected to be due to mass effect from bilateral unruptured ophthalmic segment aneurysms pressing on the olfactory tracts. Each aneurysm was treated with a Pipeline embolization device (PED). Follow-up angiography at 5 months showed occlusion of both aneurysms. The patient experienced subjective improvement in olfaction and complete objective resolution of her hyposmia as measured by the validated University of Pennsylvania Smell Identification Test (UPSIT). CONCLUSION: Intracranial aneurysms causing dysfunction of olfactory sensation due to mass effect upon the olfactory tract can be successfully treated with flow diversion. Flow diversion should be considered as one of the treatment options for patients with cranial nerve dysfunction due to unruptured intracranial aneurysms.

The functional neuroanatomy of odor evoked autobiographical memories cued by odors and words.

Behavioral evidence indicates that odor evoked autobiographical memories (OEAMs) are older, more emotional, less thought of and induce stronger time traveling characteristics than autobiographical memories (AMs) evoked by other modalities. The main aim of this study was to explore the neural correlates of AMs evoked by odors as a function of retrieval cue. Participants were screened for specific OEAMs and later presented with the odor cue and its verbal referent in an fMRI paradigm. Because the same OEAM was retrieved across both cue formats (odor and word), potential cue dependent brain activations were investigated. The overall results showed that odor and word cued OEAMs activated regions typically associated with recollection of autobiographical information. Although no odors were presented, a verbal cuing of the OEAMs activated areas associated with olfactory perception (e.g., piriform cortex). However, relative to word cuing, an odor cuing of OEAMs resulted in more activity in MTL regions such as the parahippocampus, and areas involved in visual vividness (e.g., occipital gyrus and precuneus). Furthermore, odor cues activated areas related to emotional processing, such as limbic and tempopolar regions significantly more. In contrast, word cues relative to odor cues recruited a more widespread and bilateral prefrontal activity. Hippocampus activity did not vary as function of the remoteness of the memory, but recollection of OEAMs from the 1(st) vs the 2(nd) decade of life showed specific activation in the right OFC, whereas the 2(nd) reflected a higher activation in the left inferior frontal gyrus.

Comparative morphometry of the olfactory bulb, tract and stria in the human, dog and goat / Morfometría comparada del bulbo, tracto y estría olfatoria en el humano, perro y cabra

Morphometric parameters of olfactory brain components show species-dependent variations. However, the association of these parameters with olfactory function vis-à-vis ecological and evolutionary behaviors is poorly understood. In this study, a morphometric analysis of the olfactory bulb, tract and stria was carried out in three ecologically diverse animals comprising humans (primate), dogs (carnivore) and goats (herbivore) to elucidate differences in morphometry in relation to olfactory function. Using formalin-fixed brains, volumes and linear measurements of the olfactory structures were determined and correlated with those of cerebrum and the whole brain. The volume of the olfactory bulb was greatest in dogs, followed by goats and humans and constituted 0.31 percent, 0.18 percent and 0.01 percent, respectively, of the brain volume. Similarly, the ratio of volume of the bulb, tract and stria to that of brain was 1.95 percent in the dog, 0.77 percent in the goat and 0.03 percent in the human. The width of the bulb was greatest (p< 0.05) in dogs (10.80 +/- 1.64mm) compared to goats (8.25 +/- 0.96mm) and humans (5.50 +/- 0.71mm), and accounted for a hemisphere breadth of 42.91 percent, 29.73 percent and 8.94 percent respectively. Interestingly though, the total length of the olfactory bulb, tract and striae increased in the order of goat (34.5 +/- 1.30mm), human (36.25 +/- 1.70mm) and dog (48.20 +/- 1.92mm), and constituted 21.47 percent, 51.87 percent and 72.30 percent, respectively, of the hemisphere length. These results suggest that the morphometric adaptations of the olfactory components to olfactory function decline from the dog, to goat, to human, and this may be indicative of the varied olfactory functional needs in regard to the ecological diversity of these species.

Los parámetros morfométricos de los componentes del cerebro olfativo presentan variaciones que dependen de las especies. Sin embargo, la asociación de estos parámetros con la función olfativa vis-à-vis los comportamientos ecológicos y evolutivos es poco conocida. En este estudio se llevó a cabo un análisis morfométrico del bulbo, tracto y estría olfatoria en tres animales de diversidad ecológica que abarcan los seres humanos (primates), perros (carnívoros) y cabras (herbívoros) para dilucidar las diferencias en la morfometría en relación con la función olfatoria. El uso de cerebros fijados en formalina, los volúmenes y las medidas lineales de las estructuras olfativas se determinaron y se correlacionaron con el cerebro. El volumen del bulbo olfatorio fue mayor en los perros, seguidos por cabras y seres humanos y constituyeron un 0,31 por ciento, 0,18 por ciento y 0,01 por ciento, respectivamente, del volumen del cerebro. Del mismo modo, la relación entre el volumen del bulbo, vías y estrías al del cerebro fue de 1,95 por ciento en el perro, un 0,77 por ciento en la cabra y 0,03 por ciento en el ser humano. El ancho del bulbo fue mayor (p <0,05) en los perros (10,80 +/- 1.64mm) en comparación con cabras (8,25 +/- 0.96mm) y humanos (5,50 +/- 0.71mm), y representó una total hemisférico de 42,91 por ciento, 29,73 por ciento y 8,94 por ciento respectivamente. Sin embargo, curiosamente la longitud total del bulbo olfatorio, del tracto y estrías aumentaron en la cabra (34,5 +/- 1,30 mm), en humanos (36,25 +/- 1.70mm) y en el perro (48,20 +/- 1,92mm), y constituyeron 21,47 por ciento, 51,87 por ciento y 72,30 por ciento, respectivamente, del largo del hemisferio. Estos resultados sugieren que las adaptaciones morfométricas de los componentes olfativos de la función olfativa se van reduciendo de perro a cabra y al hombre y esto puede ser indicativo de las variadas necesidades funcionales olfativas en lo que respecta a la diversidad ecológica de estas especies.

Increased limbic and brainstem activity during migraine attacks following olfactory stimulation.

OBJECTIVE: Migraine patients have dysfunctional cortical olfactory processing and very often report hypersensitivity and phobic symptoms to odors during acute headache attacks. However, imaging data of how the brain processes associate migraine symptoms, such as photophobia, phonophobia, or osmophobia, are rare. METHODS: The present study aimed to explore neuronal processing in response to olfactory stimulation (rose odor) in migraine patients in and outside acute headache attacks. Using event-related fMRI we studied 20 migraine patients and compared behavioral and imaging data with sex- and age-matched healthy controls. Additionally, 13 of the 20 patients were scanned within 6 hours after the onset of a spontaneous migraine attack. RESULTS: Imaging data showed that interictal migraineurs did not differ from control subjects. However, during spontaneous and untreated attacks, migraine patients showed significantly higher blood oxygen level-dependent signal intensities in brain areas including limbic structures (amygdala and insular cortices) and, more specifically, in the rostral pons in response to olfactory stimulation. CONCLUSIONS: Increased activity in the rostral part of the pons has previously been specifically linked to the pain of the migraine attack. The present finding suggests that the activity level of this structure can be triggered by olfactory input and thus points to the strong physiologic relationship between the olfactory and the trigemino-nociceptive pathway in the pathophysiology of migraine disease.

Altered activation patterns within the olfactory network in Parkinson's disease.

Olfactory impairment is a consistent premotor symptom in sporadic Parkinson's disease (PD), presumably caused by pathological processes in the olfactory bulb and olfactory structures within mesolimbic brain areas. The objective of the present study was to obtain an in-depth insight into olfactory network dysfunction in PD patients. Event-related functional magnetic resonance imaging (3 T) was conducted with 16 early-stage PD patients and 16 matched controls during an odor detection task. Activation within the olfactory network was analyzed both in terms of strength of activation (whole-brain random effects, regions of interest [ROI] analysis based on the hemodynamic response function) as well as time-course characteristics (finite impulse response-based ROI analysis). Olfactory-induced activation in patients with PD in comparison to a standard activation pattern obtained from controls revealed profound hyperactivation in piriform and orbitofrontal cortices. However, whereas orbitofrontal areas seem to be unable to discriminate between signal and noise, primary olfactory cortex shows preserved discriminatory ability. These results support a complex network dysfunction that exceeds structural pathology observed in the olfactory bulb and mesolimbic cortices and thus demonstrate the important contribution of functional data to describe network dynamics occurring in the degenerating brain.

Disruption of odour quality coding in piriform cortex mediates olfactory deficits in Alzheimer's disease.

Patients with early-stage Alzheimer's disease exhibit perceptual deficits in odour identification, often before the appearance of overt memory loss. This impairment coincides with the initial accumulation of pathological lesions in limbic olfactory brain regions. Although these data imply that odour stimuli may be effectively used as biological probes of limbic dysfunction, the precise neural mechanisms underlying the olfactory deficits in early Alzheimer's disease remain poorly understood. In the current study, we combined functional magnetic resonance imaging with an olfactory cross-adaptation paradigm to test the hypothesis that perceptual codes of odour quality in posterior piriform cortex are degraded in patients with Alzheimer's disease. In elderly control subjects, sequential presentation of qualitatively similar (versus qualitatively different) odourant pairs elicited cross-adapting responses in posterior piriform cortex, in accord with the pattern observed in healthy young adults. However, this profile was significantly blunted in patients with Alzheimer's disease, reflecting a functional disruption of odour quality coding in this olfactory brain area. These results highlight the potential of olfactory functional magnetic resonance imaging as a non-invasive bioassay of limbic functional integrity, and suggest that such an index could possibly aid in the early diagnosis of Alzheimer's disease. Furthermore, as a putative lesion model of odour quality processing in the human brain, our study suggests a causal role of posterior piriform cortex in differentiating olfactory objects.

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.

[Relationship between the regional cerebral blood flow and the cognitive function and anosmia in patients with Parkinson disease and Alzheimer disease].

We compared the relationship between regional cerebral blood flow (rCBF) of the olfactory area and the cognitive function and anosmia in patient with Parkinson disease (PD) and in those with Alzheimer disease (AD). UPDRS III, MMSE, HDS-R, CDR, Beck Depression Inventory (BDI) were employed in this study. The subjects included 56 PD patients (average age 71.4+/-9.69 years), 23 AD patients (average age 73.3+/-7.12 years), 12 patients with mild cognitive impairment (MCI) (average age 72.5+/-6.89 years), and 9 age-matched controls (NC) (average age 73.8+/-6.61 years). Next we intravenously injected 1 ampule of thiamine propyldisulphide (Alinamin) and confirmed anosmia. In addition, we performed 123I-IMP SPECT (SEE methods) and satistically determined rCBF of the olfactory area based on the basis of the Z scores of the interest area. Anosima was detected in approximately 40% of the PD and AD patients. The HDS-R and MMSE scores were significantly higher in patients with anosima than in those without anosima; the CDR scores were significantly higher in the former than in the latter. Further, the incidence of anosima in PD patients and AD patients with MCI increased with an increase in the CDR scores. In order to determine the rCBF of the olfactory area of the PD and AD patients. As to rCBF of the olfactory area, we examined left and right Z scores of hippocampus, parahippocampus, amygdala, and uncus at Talairach level 3 and the scores of the Brodmann area 28, 34, 35, and 36 at Talairach level 5. In patients with anosmia, the Z scores were significantly high in cases with anosmia in all areas except the right Brodmann area 34 in PD patients and the right Brodmann area 28 and bilateral the Brodmann area 34 of both sides in AD patients. Some parts of the olfactory area are closely related to cognitive function, and it appeares that a reduced rCBF in the olfactory areas may lead to a functional decline in these regions which may cause anosmia and cognitive decline in PD and AD patients.

Selective attention to affective value alters how the brain processes olfactory stimuli.

How does selective attention to affect influence sensory processing? In a functional magnetic resonance imaging investigation, when subjects were instructed to remember and rate the pleasantness of a jasmine odor, activations were greater in the medial orbito-frontal and pregenual cingulate cortex than when subjects were instructed to remember and rate the intensity of the odor. When the subjects were instructed to remember and rate the intensity, activations were greater in the inferior frontal gyrus. These top-down effects occurred not only during odor delivery but started in a preparation period after the instruction before odor delivery, and continued after termination of the odor in a short-term memory period. Thus, depending on the context in which odors are presented and whether affect is relevant, the brain prepares itself, responds to, and remembers an odor differently. These findings show that when attention is paid to affective value, the brain systems engaged to prepare for, represent, and remember a sensory stimulus are different from those engaged when attention is directed to the physical properties of a stimulus such as its intensity. This differential biasing of brain regions engaged in processing a sensory stimulus depending on whether the cognitive demand is for affect-related versus more sensory-related processing may be an important aspect of cognition and attention. This has many implications for understanding the effects not only of olfactory but also of other sensory stimuli.

Cross-modal integration of intranasal stimuli: a functional magnetic resonance imaging study.

Most odorants, in addition to the olfactory system, also activate the intranasal trigeminal system. Recent studies have shown that pure trigeminal stimulation activates somatosensory regions as well as regions traditionally thought of as primary olfactory areas. As a main aim of this study we wished to a) ascertain which brain regions are responsive to an "artificially" bimodal odor composed of a trigeminal (CO(2)) and an olfactory stimulant (phenyl ethyl alcohol, PEA) and b) determine if presenting CO(2) and PEA simultaneously activates different brain regions than when presenting them individually. Fifteen men were scanned using functional magnetic resonance imaging while smelling PEA, CO(2), and a mixture of both stimuli (CO(2)PEA) presented simultaneously. Odors were presented monorhinally to the right nostril in a block design. The contrast between CO(2)PEA and baseline revealed areas implicated in the processing of both olfactory and trigeminal stimuli. When the mixture was contrasted with the sum of its single components (CO(2)PEA-{CO(2)+PEA}), activations in integration centers (left superior temporal and right intraparietal sulcus) and in orbitofrontal areas (left medial and lateral orbitofrontal cortex) were detected. The opposite contrast ({CO(2)+PEA}-CO(2)PEA) did not reveal any significant activation. In contrast to studies which have used natural mixed olfactory/trigeminal stimuli, we have shown that the perception of an artificial mixed olfactory/trigeminal stimulus activates, as opposed to inhibiting the olfactory cortex. Further, we also conclude that a mixed olfactory/trigeminal stimulus appears to lead to higher cortical activations than the sum of its parts.

Human brain activation in response to olfactory stimulation by intravenous administration of odorants.

To identify the BOLD effects related to olfaction in humans, we recorded functional magnetic resonance imaging (fMRI) scans in response intravenously instilled thiamine propyl disulfide (TPD) and thiamine tetrahydrofurfuryl disulfide monohydrochloride (TTFD). TPD and TTFD evoked a strong and weak odor sensation, respectively. Since we did not spray the odor stimuli directly, this method is expected to reduce the effect caused by direct stimulation of the trigeminal nerve. For the analysis of fMRI data, statistical parametric mapping (SPM2) was employed and the areas significantly activated during olfactory processing were located. Both strong and weak odorants induced brain activities mainly in the orbitofrontal gyrus (Brodmann's area: BA 11) in the left hemisphere. TPD (a strong odorant) induced activity in the subthalamic nucleus in the left hemisphere and the precentral gyrus (BA 6) and insula in the right hemisphere. TTFD (a weak odorant) induced activity in the superior frontal gyrus (BA 11) in the right hemisphere. In both circumstances, there was an increase in blood flow at the secondary olfactory cortex (SOC) but not the primary olfactory cortex (POC), probably due to a habituation effect in the POC. From the present results, we found brain activity in not only odor-specific regions but also regions whose levels of activity were changed by an intensity difference of odor stimuli.

Umami: a delicious flavor formed by convergence of taste and olfactory pathways in the human brain.

Umami taste is produced by glutamate acting on a fifth taste system. However, glutamate presented alone as a taste stimulus is not highly pleasant, and does not act synergistically with other tastes (sweet, salt, bitter and sour). We show here that when glutamate is given in combination with a consonant, savory, odour (vegetable), the resulting flavor can be much more pleasant. Moreover, we showed using functional brain imaging with fMRI that the glutamate taste and savory odour combination produced much greater activation of the medial orbitofrontal cortex and pregenual cingulate cortex than the sum of the activations by the taste and olfactory components presented separately. Supralinear effects were much less (and significantly less) evident for sodium chloride and vegetable odour. Further, activations in these brain regions were correlated with the pleasantness and fullness of the flavor, and with the consonance of the taste and olfactory components. Supralinear effects of glutamate taste and savory odour were not found in the insular primary taste cortex. We thus propose that glutamate acts by the nonlinear effects it can produce when combined with a consonant odour in multimodal cortical taste-olfactory convergence regions. We propose the concept that umami can be thought of as a rich and delicious flavor that is produced by a combination of glutamate taste and a consonant savory odour. Glutamate is thus a flavor enhancer because of the way that it can combine supralinearly with consonant odours in cortical areas where the taste and olfactory pathways converge far beyond the receptors.

Functional optical hemodynamic imaging of the olfactory cortex.

OBJECTIVE: We used multichannel near-infrared spectroscopy (MNIRS) to monitor the activity of the frontal cortex as mirrored by hemodynamic responses subjected to olfactory stimulation. The aim of this study was to clarify the functional brain imaging of olfactory activity. STUDY DESIGN: Prospective study. METHODS: This study was conducted on eight healthy subjects aged from 22 to 39 years (4 men and 4 women; mean age, 28.8 yr). We used a 22-channel near-infrared spectroscopy device with eight light-incident fibers and seven detector fibers, each with an interoptode distance of 2.5 cm on the frontal region. Olfactory stimulation consisted of five repetitions, each lasting 5 seconds and followed by a 55 seconds rest period. Isovaleric acid was used as odor stimulation, and saline was used as a control. We measured the changes in concentrations of oxyhemoglobin [oxyHb], deoxyhemoglobin [deoxyHb], and total hemoglobin [totalHb] from prebaseline values. Furthermore, we divided the frontal cortex into four areas (right upper, left upper, right lower, left lower) and investigated the activity in each area. RESULTS: Isovaleric acid caused changes, especially in the lower area, but saline caused no changes. [oxyHb] and [totalHb] increased after odor stimulation, but [deoxyHb] did not change. These active areas may be related to the orbitofrontal cortex, corresponding to olfactory cortices. CONCLUSION: This study has shown that MNIRS enables evaluation of changes in hemodynamics related to brain activity by olfactory stimulation.

Positron tomographic emission study of olfactory induced emotional recall in veterans with and without combat-related posttraumatic stress disorder.

OBJECTIVE: Memory for odors is often associated with highly emotional experiences, and odors have long been noted by clinicians to be precipitants of trauma symptoms in posttraumatic stress disorder (PTSD). Primitive brain systems involved in fear responsivity and survival also mediate smell, including the olfactory cortex and amygdala. The purpose of this study was to measure neural correlates of olfaction in PTSD. METHODS: We exposed male combat veterans with PTSD (N = 8) and without PTSD (N = 8) to a set of smells, including diesel (related to traumatic memories of combat), and three other types of smells: odorless air, vanilla/coconut, and hydrogen sulfide (H2S) (respectively, a neutral, positive, and negative hedonic nontraumatic smell) in conjunction with PET imaging of cerebral blood flow and assessment of psychophysiological and behavioral symptoms. All subjects also underwent a baseline of olfactory acuity. RESULTS: PTSD patients rated diesel as unpleasant and distressing, resulting in increased PTSD symptoms and anxiety in PTSD versus combat controls. Exposure to diesel resulted in an increase in regional blood flow (rCBF) in amygdala, insula, medial prefrontal cortex, and anterior cingulate cortex, and decreased rCBF in lateral prefrontal cortex in PTSD in comparison to combat controls. Combat controls showed less rCBF changes on any smell, and did not show amygdala activation upon diesel exposure. CONCLUSIONS: These data support the hypothesis that in PTSD trauma-related smells can serve as strong emotional reminders. The findings indicate the involvement of a neural circuitry that shares olfactory elements and memory processing regions when exposed to trauma-related stimuli.

Dissociated representations of irritation and valence in human primary olfactory cortex.

Irritation and negative valence are closely associated in perception. However, these perceptual aspects can be dissociated in olfaction where irritation can accompany both pleasant and unpleasant odorants. Whereas the sensation of odor reflects transduction at olfactory receptors, irritation reflects concurrent transduction of the odorant at trigeminal receptors. Thus a stimulus can be either a pure olfactant activating the olfactory receptors only or a bimodal odorant activating both types of receptors. Using event-related functional magnetic resonance imaging and a 2 x 2 experimental design contrasting odorant valence (pleasant/unpleasant) and odorant type (pure olfactant/bimodal) we found activity in piriform cortex to be associated with valence, and not type, of odors. In contrast, activity in the olfactory tubercle was associated with type, and not valence, of odors. Importantly, this was found when perceived intensity was held equal across odorants. These findings suggest that dissociable neural substrates subserve the encoding of irritation and valence in olfaction.