Time course of odorant-induced activation in the human primary olfactory cortex

Paradoxically, attempts to visualize odorant-induced functional magnetic resonance imaging (fMRI) activation in the human have yielded activations in secondary olfactory regions but not in the primary olfactory cortex-piriform cortex. We show that odorant-induced activation in primary olfactory cortex was not previously made evident with fMRI because of the unique time course of activity in this region: in primary olfactory cortex, odorants induced a strong early transient increase in signal amplitude that then habituated within 30-40 s of odorant presence. This time course of activation seen here in the primary olfactory cortex of the human is almost identical to that recorded electrophysiologically in the piriform cortex of the rat. Mapping activation with analyses that are sensitive to both this transient increase in signal amplitude, and temporal-variance, enabled us to use fMRI to consistently visualize odorant-induced activation in the human primary olfactory cortex. The combination of continued accurate odorant detection at the behavioral level despite primary olfactory cortex habituation at the physiological level suggests that the functional neuroanatomy of the olfactory response may change throughout prolonged olfactory stimulation.     

Comparison of matched BOLD and FAIR 4.0T-fMRI with [15O]water PET brain volumes.

Valid comparisons of functional activation volumes from fMRI and PET require accurate registration, matched spatial resolution, and if possible matched noise. We coregistered 4.0T-fMRI and PET volumes, using a series of linear and nonlinear transformations applied to the PET volumes. Because of the limited number of fMRI slices that were available, PET volumes were transformed to the fMRI space. Since 4.0T-fMRI and 4.0T-MRI volumes have significant spatial distortion due to magnet inhomogeneities, high resolution 1.5T-MRI volumes were nonlinearly transformed to 4.0T-MRI volumes as part of the transformation chain. The smoothing effects of these registration transformations were measured, in order to match the spatial resolution of the coregistered fMRI and PET volumes. Spatial resolution of the transformed PET volumes in the fMRI space was degraded by up to 60% due to the transformation process. Due to both the image acquisition characteristics and the coregistration process, the transformed PET volumes had a spatial resolution that was lower than that of tMRI. Therefore, significant smoothing of fMRI volumes was necessary to match their spatial resolution with that of the transformed PET volumes. Matching the spatial resolution of the fMRI volumes to those of the transformed PET volumes was achieved by matching the shape of their point spread functions. In order to do this, Gaussian kernels were employed to smooth the fMRI volumes. We were unable to simultaneously match the resolution and noise of fMRI and PET signals in the motor cortex. Activation maps derived from transformed PET and smoothed fMRI volumes were compared. Contralateral motor cortex was active in all modalities but there were large variations in the size of the activated region and its signal to noise ratio across BOLD, FAIR, and PET images within each subject. Nevertheless, the relative CBF changes measured by FAIR were consistent with those determined by PET.     

Activity-induced manganese-dependent functional MRI of the rat visual cortex following intranasal manganese chloride administration

Manganese-enhanced MRI (MEMRI) of the brain requires delivery of manganese into the target brain regions. It was previously shown that, following intranasal application, ongoing olfactory stimulation facilitates manganese transport along the olfactory nerve into the olfactory bulb, so bypassing the blood–brain barrier (BBB). We report on experiments to evaluate whether visual stimulation can permit manganese transport onwards from the olfactory bulb to the visual cortex. Rats in intact olfactory bulb group were reserved intact olfactory bulb, while those in olfactory bulbectomy group received bilateral bulbectomy. After intranasal MnCl₂ administration, olfactory and visual stimulations were performed on all the animals for a consecutive 20 h. The visual cortex was then examined using MEMRI. Enhanced imaging on T1WI was noted in the visual cortex of the intact olfactory bulb group. Image subtraction revealed that the signal intensity in the visual cortex of the intact olfactory bulb group was significantly higher than that of olfactory bulbectomy group. Volume of interest (VOI) analysis also showed that normalized intensities in the visual cortex of the intact olfactory bulb group were significantly higher as compared with those of the olfactory bulbectomy group. Inductively coupled plasma mass spectrometry (ICP-MS) confirmed that the manganese content in the visual cortex of the intact olfactory bulb group was increased in comparison with that of the olfactory bulbectomy group. These findings indicate that activity-induced manganese-dependent functional MRI (AIM fMRI) of the rat visual cortex can be performed following intranasal administration of manganese and demonstrate that manganese can migrate from the olfactory bulb to the visual cortex.     

Attentional modulation in human primary olfactory cortex

Central to the concept of attention is the fact that identical stimuli can be processed in different ways. In olfaction, attention may designate the identical flow of air through the nose as either respiration or olfactory exploration. Here we have used functional magnetic resonance imaging (fMRI) to probe this attentional mechanism in primary olfactory cortex (POC). We report a dissociation in POC that revealed attention-dependent and attention-independent subregions. Whereas a temporal subregion comprising temporal piriform cortex (PirT) responded equally across conditions, a frontal subregion comprising frontal piriform cortex (PirF) and the olfactory tubercle responded preferentially to attended sniffs as opposed to unattended sniffs. In addition, a task-specific anticipatory response occurred in the attention-dependent region only. This dissociation was consistent across two experimental designs: one focusing on sniffs of clean air, the other focusing on odor-laden sniffs. Our findings highlight the role of attention at the earliest cortical levels of olfactory processing.     

Olfactory-induced brain activity in Parkinson's disease relates to the expression of event-related potentials: a functional magnetic resonance imaging study

Olfactory disorders are common in patients with idiopathic Parkinson's disease (IPD). In IPD patients with hyposmia olfactory event-related potentials (ERPs) are typically found to be delayed or absent. Altered ERPs in IPD patients may also be consistent with reduced neuronal activity in the medial temporal lobe following olfactory stimulation, as demonstrated by functional magnetic resonance imaging (fMRI). We analyzed ERPs and fMRI scans of hyposmic IPD patients (n=18) to gain further insight about the brain regions involved in generation of olfactory ERPs. Patients were separated into two groups (n=9 per group), based on the detectability (+) or non-detectability (−) of ERPs. Central activation during olfactory stimulation was examined using fMRI. Both ERP+ and ERP− patients showed activity in brain areas relevant to olfactory processing, such as the amygdala, parahippocampal regions, and temporal regions (BA 37, 21/22). Comparison of both groups revealed higher activation in ERP+ patients, especially in the amygdala, parahippocampal cortex, inferior frontal gyrus (BA 47), insula, cingulate gyrus, striatum, and inferior temporal gyrus. The relationship between the expression of olfactory ERPs and cortical activation patterns seen during olfactory stimulation in fMRI in IPD patients supports the idea that ERPs are a sensitive marker of neurodegeneration in olfactory regions. In accordance with current neuropathological staging concepts, olfactory ERPs may be reflecting pathological changes in olfactory regions, independent of the typically observed nigro-striatal degeneration in IPD. Reduced activation of primary olfactory areas in the ERP-group may reflect a severe disruption of olfactory processing in these patients.     

Olfactory input is critical for sustaining odor quality codes in human orbitofrontal cortex

Ongoing sensory input is critical for shaping internal representations of the external world. Conversely, a lack of sensory input can profoundly perturb the formation of these representations. The olfactory system is particularly vulnerable to sensory deprivation, owing to the widespread prevalence of allergic, viral and chronic rhinosinusitis, but how the brain encodes and maintains odor information under such circumstances remains poorly understood. Here we combined functional magnetic resonance imaging (fMRI) with multivariate (pattern-based) analyses and psychophysical approaches to show that a 7-d period of olfactory deprivation induces reversible changes in odor-evoked fMRI activity in piriform cortex and orbitofrontal cortex (OFC). Notably, multivoxel ensemble codes of odor quality in OFC became decorrelated after deprivation, and the magnitude of these changes predicted subsequent olfactory perceptual plasticity. Our findings suggest that transient changes in these key olfactory brain regions are instrumental in sustaining odor perception integrity in the wake of disrupted sensory input.     

A multimodal MR-compatible olfactometer with real-time controlling capability

Abstract

Design of an MR-compatible and computer-controlled odour stimuli system is essential in the studies of human olfactory function. Olfactometers are used to deliver odours to the subjects in an objective manner. We present a portable, computer-controlled eight channels olfactometer able to stimulate olfaction by employing liquid odorant stimuli. We used a high-pressure pump to generate medical grade airflow. After passing through solenoid valve-controlled odour reservoirs, odorant stimulus is conveyed to the nasal mask. The odour delivery delay of the device was measured using photo-ionisation detectors. To assess the application of the designed olfactometer, an fMRI experiment was done with 9 healthy subjects. Two odour stimuli (Vanillin and Rose) were presented to each subject in an alternating block design task of odour and non-odour conditions. The response time of each subject was gathered using the response box. Group analysis revealed a significant BOLD signal change in some regions of olfactory and trigeminal networks including the orbitofrontal cortex, insula, inferior frontal gyrus, hippocampus, cingulate gyrus and piriform cortex. The odour delivery delay measured by photo-ionisation detector was 190?ms, and the subjects’ response showed 205?ms for the Vanillin and 243?ms for the Rose odour stimuli. Our portable MR-compatible olfactometer as a stimulation device is capable of creating adequate stimulation suitable for olfactory fMRI experiments.     

What does neuroimaging tell us about the role of prefrontal cortex in memory retrieval?

The past five years have seen an outpouring of neuroimaging studies of memory — using both positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). These studies have convincingly demonstrated that neuroimaging can be used to study the functional anatomy of normal human memory and that neuroimaging can precisely localize memory related brain activations within small areas of cortex. As one illustration of the application of neuroimaging in the study of memory, this review shows how several laboratories have produced data that converge on the notion that specific areas in the prefrontal cortex are active during long-term memory retrieval. Moreover, the data further suggest that distinct prefrontal brain areas might make differential contributions to different kinds of long-term memory retrieval.     

Functional mapping of human brain in olfactory processing: a PET study

This study describes the functional anatomy of olfactory and visual naming and matching in humans, using positron emission tomography (PET). One baseline control task without olfactory or visual stimulation, one control task with simple olfactory and visual stimulation without cognition, one set of olfactory and visual naming tasks, and one set of olfactory and visual matching tasks were administered to eight normal volunteers. In the olfactory naming task (ON), odors from familiar items, associated with some verbal label, were to be named. Hence, it required long-term olfactory memory retrieval for stimulus recognition. The olfactory matching task (OM) involved differentiating a recently encoded unfamiliar odor from a sequentially presented group of unfamiliar odors. This required short-term olfactory memory retrieval for stimulus differentiation. The simple olfactory and visual stimulation resulted in activation of the left orbitofrontal region, the right piriform cortex, and the bilateral occipital cortex. During olfactory naming, activation was detected in the left cuneus, the right anterior cingulate gyrus, the left insula, and the cerebellum bilaterally. It appears that the effort to identify the origin of an odor involved semantic analysis and some degree of mental imagery. During olfactory matching, activation was observed in the left cuneus and the cerebellum bilaterally. This identified the brain areas activated during differentiation of one unlabeled odor from the others. In cross-task analysis, the region found to be specific for olfactory naming was the left cuneus. Our results show definite recruitment of the visual cortex in ON and OM tasks, most likely related to imagery component of these tasks. The cerebellar role in cognitive tasks has been recognized, but this is the first PET study that suggests that the human cerebellum may have a role in cognitive olfactory processing as well.     

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.     

Dopamine D1 receptors and age differences in brain activation during working memory

In an fMRI study, 20 younger and 20 healthy older adults were scanned while performing a spatial working-memory task under two levels of load. On a separate occasion, the same subjects underwent PET measurements using the radioligand [¹¹C] SCH23390 to determine dopamine D₁ receptor binding potential (BP) in caudate nucleus and dorsolateral prefrontal cortex (DLPFC). The fMRI study revealed a significant load modulation of brain activity (higher load > lower load) in frontal and parietal regions for younger, but not older, adults. The PET measurements showed marked age-related reductions of D₁ BP in caudate and DLPFC. Statistical control of caudate and DLPFC D₁ binding eliminated the age-related reduction in load-dependent BOLD signal in left frontal cortex, and attenuated greatly the reduction in right frontal and left parietal cortex. These findings suggest that age-related alterations in dopaminergic neurotransmission may contribute to underrecruitment of task-relevant brain regions during working-memory performance in old age.     

Neural coding of stimulus concentration in the human olfactory and intranasal trigeminal systems

Nasal chemical sensations are mediated principally by the olfactory and the trigeminal systems. Over the last few years brain structures involved in processing of trigeminal stimuli have been more and more documented. However, the exact role of individual regions in stimulus intensity processing is unclear. The present study set out to examine the neural network involved in encoding stimulus intensity in the trigeminal system and the olfactory system of humans. Participants were presented with two concentrations of relatively specific trigeminal stimuli (CO2) and olfactory (H2S), respectively. Responses were assessed by functional magnetic resonance imaging (fMRI). Whereas brain responses to stimulus intensity in the olfactory modality involved a wide neural network including cerebellum, entorhinal cortex, visual areas, and frontal regions, contrasting high and low CO2 concentrations revealed activation in a less complex network including various sub-regions of the cingulate cortex. Taken together, these results suggest separate but overlapping neural networks involved in encoding stimulus intensity in the two chemosensory systems.     

人脑对食物视觉刺激反应的功能磁共振成像的任务模式研究

虽然正电子发射断层成像 (positronemissiontomography ,PET)实验研究证明 ,杏仁核、眶额皮质与人脑在饥饿状态下对食物视觉刺激反应相关 ,但它对人体有微创、时间分辨率低、成本高的缺陷限制了人们在这方面的进一步研究。功能磁共振成像克服了这些缺陷 ,并且它的数据可以单例处理。但它的实验设计比PET的复杂 ,目前也没有较多任务模式设计经验可以借鉴。因此 ,要进行这方面的预实验。 5名健康志愿受试者随机分 3组 ,选择组块、事件相关和快速事件相关任务模式中的一种 ,禁食 12h后扫描。成像过程中 ,受试者接受随机播放的食物图片、非食物图片和空白模糊图片的视觉刺激。再采用SPM2软件处理功能像数据。对感兴趣的食品图片与中性物品图片的对比、食品图片与空白对照组图片对比的相关功能区域进行了t检验后发现 ,事件相关任务模式所得到的相关功能区 ,比其他两类任务模式的相应区域较多地包含了杏仁核、眶额皮质区 ,与既往PET的实验结果相符程度最大。可见事件相关任务模式是一种相对稳定的功能成像模式。     

Brain imaging studies of cocaine abuse: implications for medication development

Contemporary in vivo brain imaging techniques confer the ability to assess brain function and structure noninvasively, and thereby can yield information to help guide the development of new treatments for substance abuse. The advantages and limitations of the major imaging modalities (positron emission tomography [PET], single photon emission computed tomography [SPECT], structural and functional magnetic resonance imaging [MRI, fMRI, respectively]) are discussed with respect to their applicability to research on cocaine abuse. The effects of acute administration of cocaine have been studied using PET and fMRI, with PET manifesting decreases in cerebral glucose metabolism and blood flow, and fMRI revealing regional effects that are correlated temporally with subjective responses. In addition, studies of drug abusers, abstinent from cocaine for various lengths of time, have revealed persistent differences in brain function and structure, especially in the frontal cortex, when compared with parameters in the brains of subjects who do not use illicit drugs of abuse. PET studies also have revealed abnormalities in markers for dopaminergic and opioid systems during withdrawal from cocaine. Moreover, studies of cue-elicited craving for cocaine demonstrate a connection between the response to drug-related stimuli and neural elements of cognition and emotion. The future directions of in vivo brain imaging to identify functional and structural alterations in the brains of cocaine abusers are discussed in relation to the development of medications to treat cocaine dependence.     

The development of antisocial behavior: what can we learn from functional neuroimaging studies?

The recent development of low-risk imaging technologies, such as functional magnetic resonance imaging (fMRI), have had a significant impact on the investigation of psychopathologies in children and adolescents. This review considers what we can infer from fMRI work regarding the development of conduct disorder (CD) and oppositional defiant disorder (ODD). We make two central assumptions that are grounded in the empirical literature. First, the diagnoses of CD and ODD identify individuals with heterogeneous pathologies; that is, different developmental pathologies can receive a CDD or ODD diagnosis. This is indicated by the comorbidities associated with CD/ODD, some of which appear to be mutually exclusive at the biological level (e.g., posttraumatic stress disorder [PTSD] and psychopathic tendencies). Second, two populations of antisocial individuals can be identified: those that show an increased risk for only reactive aggression and those that show an increased risk for both reactive and instrumental aggression. We review the fMRI data indicating that particular comorbidities of CD/ODD (i.e., mood and anxiety conditions such as childhood bipolar disorder and PTSD) are associated with either increased responsiveness of neural regions implicated in the basic response to threat (e.g., the amygdala) or decreased responsiveness in regions of frontal cortex (e.g., ventromedial frontal cortex) that are implicated in the regulation of the basic threat response. We suggest why such pathology would increase the risk for reactive aggression and, in turn, lead to the association with a CD/ODD diagnosis. We also review the literature on psychopathic tendencies, a condition where the individual is at significantly elevated risk for both reactive and instrumental aggression. We show that in individuals with psychopathic tendencies, the functioning of the amygdala in stimulus-reinforcement learning and of the ventromedial frontal cortex in the representation of reinforcement expectancies is impaired. We suggest why such pathology would increase the risk for reactive and instrumental aggression and thus also lead to the association with a CD/ODD diagnosis.     

Different brain structures related to self- and external-agency attribution: a brief review and meta-analysis

Several neuroimaging studies have consistently shown activations of areas surrounding the temporo-parietal junction (TPJ) during tasks exploring the sense of agency. Beyond TPJ, activations in different structures, such as the dorsolateral prefrontal cortex (dLPFC), the pre-supplementary motor area (pre-SMA), the insula and the precuneus have been reported. Moreover, a possible dissociation between self- and external-agency attribution has been suggested. To test the hypothesis of distinct neural correlates for self- and external-agency attribution a quantitative meta-analysis, based on activation likelihood estimation (ALE) method, across 15 PET and fMRI studies (228 subjects) was conducted. Results show converging activations including the TPJ, pre-SMA, precuneus and dorsomedial prefrontal cortex (dMPFC) in external-agency, while insula activation was related to self-agency. We discuss these findings, highlighting the role of the insula, and calling for the use of alternative paradigms such as intentional binding and interactive imitation to study agency.     

Localization of asymmetric brain function in emotion and depression

Although numerous EEG studies have shown that depression is associated with abnormal functional asymmetries in frontal cortex, fMRI and PET studies have largely failed to identify specific brain areas showing this effect. The present study tested the hypothesis that emotion processes are related to asymmetric patterns of fMRI activity, particularly within dorsolateral prefrontal cortex (DLPFC). Eleven depressed and 18 control participants identified the color in which pleasant, neutral, and unpleasant words were printed. Both groups showed a leftward lateralization for pleasant words in DLPFC. In a neighboring DLPFC area, the depression group showed more right‐lateralized activation than controls, replicating EEG findings. These data confirm that emotional stimulus processing and trait depression are associated with asymmetric brain functions in distinct subregions of the DLPFC that may go undetected unless appropriate analytic procedures are used.     

Feelings of warmth correlate with neural activity in right anterior insular cortex

The neural coding of perception can differ from that for the physical attributes of a stimulus. Recent studies suggest that activity in right anterior insular cortex may underlie thermal perception, particularly that of cold. We now examine whether this region is also important for the perception of warmth. We applied cutaneous warm stimuli on the left leg (warmth) in normal subjects (n = 7) during functional magnetic resonance imaging (fMRI). After each stimulus, subjects rated their subjective intensity of the stimulus using a visual analogue scale (VAS), and correlations were determined between the fMRI signal and the VAS ratings. We found that intensity ratings of warmth correlated with the fMRI signal in the right (contralateral to stimulation) anterior insular cortex. These results, in conjunction with previous reports, suggest that the right anterior insular cortex is important for different types of thermal perception.     

The role of the dorsolateral prefrontal cortex in deception when remembering neutral and emotional events

We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of deception while remembering neutral events and emotional events. Before fMRI, subjects were presented with a series of neutral and emotional pictures and were asked to rate each picture for arousal. During fMRI, subjects were presented with the studied and nonstudied pictures and were asked to make an honest recognition judgment in response to half of the pictures and a dishonest response to the remaining half. We found that deception pertaining to the memory of neutral pictures was associated with increased activity in the bilateral dorsolateral prefrontal cortex, the left ventrolateral prefrontal cortex, and the left orbitofrontal cortex. We also found that deception while remembering emotional pictures was associated with increased activity in the bilateral dorsolateral prefrontal cortex. An overlapping activation between the two types of deception was found in the bilateral dorsolateral prefrontal cortex. Our results indicate that the dorsolateral prefrontal cortex is associated with the executive aspects of deception, regardless of the emotional valence of memory content.     

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.