Parenting behaviors in mice: Olfactory mechanisms and features in models of autism spectrum disorders.

Rodents, along with numerous other mammals, heavily depend on olfactory cues to navigate their social interactions. Processing of olfactory sensory inputs is mediated by conserved brain circuits that ultimately trigger social behaviors, such as social interactions and parental care. Although innate, parenting is influenced by internal states, social experience, genetics, and the environment, and any significant disruption of these factors can impact the social circuits. Here, we review the molecular mechanisms and social circuits from the olfactory epithelium to central processing that initiate parental behaviors and their dysregulations that may contribute to the social impairments in mouse models of autism spectrum disorders (ASD). We discuss recent advances of the crucial role of olfaction in parental care, its consequences for social interactions, and the reciprocal influence on social interaction impairments in mouse models of ASD.

Alterations in Piriform and Bulbar Activity/Excitability/Coupling Upon Amyloid-ß Administration in vivo Related to Olfactory Dysfunction.

BACKGROUND: Deficits in odor detection and discrimination are premature symptoms of Alzheimer's disease (AD) that correlate with pathological signs in the olfactory bulb (OB) and piriform cortex (PCx). Similar olfactory dysfunction has been characterized in AD transgenic mice that overproduce amyloid-ß peptide (Aß), which can be prevented by reducing Aß levels by immunological and pharmacological means, suggesting that olfactory dysfunction depends on Aß accumulation and Aß-driven alterations in the OB and/or PCx, as well as on their activation. However, this possibility needs further exploration. OBJECTIVE: To characterize the effects of Aß on OB and PCx excitability/coupling and on olfaction. METHODS: Aß oligomerized solution (containing oligomers, monomers, and protofibrils) or its vehicle were intracerebroventricularlly injected two weeks before OB and PCx excitability and synchrony were evaluated through field recordings in vivo and in brain slices. Synaptic transmission from the OB to the PCx was also evaluated in slices. Olfaction was assessed through the habituation/dishabituation test. RESULTS: Aß did not affect lateral olfactory tract transmission into the PCx but reduced odor habituation and cross-habituation. This olfactory dysfunction was related to a reduction of PCx and OB network activity power in vivo. Moreover, the coherence between PCx-OB activities was also reduced by Aß. Finally, Aß treatment exacerbated the 4-aminopyridine-induced excitation in the PCx in slices. CONCLUSION: Our results show that Aß-induced olfactory dysfunction involves a complex set of pathological changes at different levels of the olfactory pathway including alterations in PCx excitability and its coupling with the OB. These pathological changes might contribute to hyposmia in AD.

Functional Alterations in the Olfactory Neuronal Circuit Occur before Hippocampal Plasticity Deficits in the P301S Mouse Model of Tauopathy: Implications for Early Diagnosis and Translational Research in Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by neuronal loss and impaired synaptic transmission, ultimately leading to cognitive deficits. Early in the disease, the olfactory track seems most sensitive to tauopathy, while most plasticity studies focused on the hippocampal circuits. Functional network connectivity (FC) and long-term potentiation (LTP), considered as the plasticity substrate of learning and memory, were longitudinally assessed in mice of the P301S model of tauopathy following the course (time and location) of progressively neurodegenerative pathology (i.e., at 3, 6, and 9 months of age) and in their wild type (WT) littermates. Using in vivo local field potential (LFP) recordings, early (at three months) dampening in the gamma oscillatory activity and impairments in the phase-amplitude theta-gamma coupling (PAC) were found in the olfactory bulb (OB) circuit of P301S mice, which were maintained through the whole course of pathology development. In contrast, LFP oscillatory activity and PAC indices were normal in the entorhinal cortex, hippocampal CA1 and CA3 nuclei. Field excitatory postsynaptic potential (fEPSP) recordings from the Shaffer collateral (SC)-CA1 hippocampal stratum pyramidal revealed a significant altered synaptic LTP response to high-frequency stimulation (HFS): at three months of age, no significant difference between genotypes was found in basal synaptic activity, while signs of a deficit in short term plasticity were revealed by alterations in the fEPSPs. At six months of age, a slight deviance was found in basal synaptic activity and significant differences were observed in the LTP response. The alterations in network oscillations at the OB level and impairments in the functioning of the SC-CA1 pyramidal synapses strongly suggest that the progression of tau pathology elicited a brain area, activity-dependent disturbance in functional synaptic transmission. These findings point to early major alterations of neuronal activity in the OB circuit prior to the disturbance of hippocampal synaptic plasticity, possibly involving tauopathy in the anomalous FC. Further research should determine whether those early deficits in the OB network oscillations and FC are possible mechanisms that potentially promote the emergence of hippocampal synaptic impairments during the progression of tauopathy.

The human olfactory system in two proteinopathies: Alzheimer's and Parkinson's diseases.

Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative disorders. Their etiologies are idiopathic, and treatments are symptomatic and orientated towards cognitive or motor deficits. Neuropathologically, both are proteinopathies with pathological aggregates (plaques of amyloid-ß peptide and neurofibrillary tangles of tau protein in Alzheimer's disease, and Lewy bodies mostly composed of α-synuclein in Parkinson's disease). These deposits appear in the nervous system in a predictable and accumulative sequence with six neuropathological stages. Both disorders present a long prodromal period, characterized by preclinical signs including hyposmia. Interestingly, the olfactory system, particularly the anterior olfactory nucleus, is initially and preferentially affected by the pathology. Cerebral atrophy revealed by magnetic resonance imaging must be complemented by histological analyses to ascertain whether neuronal and/or glial loss or neuropil remodeling are responsible for volumetric changes. It has been proposed that these proteinopathies could act in a prion-like manner in which a misfolded protein would be able to force native proteins into pathogenic folding (seeding), which then propagates through neurons and glia (spreading). Existing data have been examined to establish why some neuronal populations are vulnerable while others are resistant to pathology and to what extent glia prevent and/or facilitate proteinopathy spreading. Connectomic approaches reveal a number of hubs in the olfactory system (anterior olfactory nucleus, olfactory entorhinal cortex and cortical amygdala) that are key interconnectors with the main hubs (the entorhinal-hippocampal-cortical and amygdala-dorsal motor vagal nucleus) of network dysfunction in Alzheimer's and Parkinson's diseases.

Chemical intolerance: involvement of brain function and networks after exposure to extrinsic stimuli perceived as hazardous.

BACKGROUND: Chemical intolerance (CI) is a chronic condition characterized by recurring and severe symptoms triggered by exposure to low levels of odorous or pungent substances. The etiology of CI has been a controversial subject for a long time. The aim of this review is to summarize findings on the neurological processing of sensory information during and after exposure to low levels of odorous or pungent substances in individuals with CI, focusing on the brain function and networks. METHODS: Scientific studies on CI published between 2000 and 2019 in academic peer-reviewed journals were systematically searched using medical and scientific literature databases. Only peer-reviewed articles reporting original research from experimental human studies directly associated with CI, and involving related neurological responses or brain imaging after exposure to odorous or pungent substances (i.e., in chemical provocation tests), were considered. RESULTS: Forty-seven studies were found to be eligible for a full-text review. Twenty-three studies met the selection criteria and were included in this review. Evidence indicated that differences between subjects with CI and healthy controls were observed by brain imaging during and after exposure to odorous or pungent substances. Differences in brain imaging were also observed between initial exposure and after exposure to these substances. Neurological processing of sensory information after exposure to extrinsic stimuli in the limbic system and related cortices were altered in subjects with CI. A previous documentable exposure event was likely to be involved in this alteration. CONCLUSIONS: This review documents consistent evidence for the altered neurological processing of sensory information in individuals with CI. Further neurophysiological research exploring the processing of extrinsic stimuli and cognition of sensation through the limbic system and related cortices in CI, and the appearance of symptoms in individuals with CI, are required.

Human umbilical cord blood plasma alleviates age-related olfactory dysfunction by attenuating peripheral TNF-α expression.

Social requirements are needed for living in an aging society and individual longevity. Among them, improved health and medical cares, appropriate for an aging society are strongly demanded. Human cord blood-derived plasma (hUCP) has recently emerged for its unique anti-aging effects. In this study, we investigated brain rejuvenation, particularly olfactory function, that could be achieved by a systemic administration of young blood and its underlying mechanisms. Older than 24-month-old mice were used as an aged group and administered with intravenous injection of hUCP repetitively, eight times. Anti-aging effect of hUCP on olfactory function was evaluated by buried food finding test. To investigate the mode of action of hUCP, brain, serum and spleen of mice were collected for further ex vivo analyses. Systemic injection of hUCP improved aging-associated olfactory deficits, reducing time for finding food. In the brain, although an infiltration of activated microglia and its expression of cathepsin S remarkably decreased, significant changes of proinflammatory factors were not detected. Conversely, peripheral immune balance distinctly switched from predominance of Type 1 helper T (Th1) cells to alternative regulatory T cells (Tregs). These findings indicate that systemic administration of hUCP attenuates age-related neuroinflammation and subsequent olfactory dysfunction by modulating peripheral immune balance toward Treg cells, suggesting another therapeutic function and mechanism of hUCP administration. [BMB Reports 2019; 52(4): 259-264].

Hypodipsic-hypernatremia syndrome in an adult with polycythemia: a case report.

BACKGROUND: Hypernatremia is a very common electrolyte disorder and is frequently encountered in out-patient as well as in-hospital settings. We describe an adult who was found to have unexplained relative polycythemia and episodic hypernatremia. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and the patient was managed with a water-drinking schedule. CASE PRESENTATION: A 24-year-old South African-Indian man was found to have polycythemia in association with episodes of hypernatremia. Investigations indicated that he had relative polycythemia. He experienced no thirst at a time when his serum sodium concentration was found to be 151 mmol/L. Further testing indicated that his renal response to arginine vasopressin was intact and magnetic resonance imaging of his brain revealed no hypothalamic lesions. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and he was managed with a water-drinking schedule that corrected his hypernatremia. CONCLUSION: Hypodipsia should always be considered when a patient without physical or cognitive disability presents with unexplained episodic hypernatremia or with relative polycythemia.

Prenatal bisphenol A exposure is associated with medial amygdala neuron hyperresponsiveness to predator odor in rats.

Perinatal exposure to bisphenol A (BPA) causes several alterations in brain function and behavior. In previous studies, we showed that prenatal treatment with low-level BPA impaired gender-specific behavior, enhanced depression-like behavior, and augmented behavioral responses to predator odor in rats. On this premise, we hypothesized that BPA-treated rats were more susceptible to predator odor stress. To test the potential neural mechanism underlying this effect, we conducted an electrophysiological study of neurons in the medial amygdala-a regional component of the olfactory pathway with high estrogen and androgen receptor expression, and thus a potential target of BPA-in rats exposed to BPA. Extracellular recordings were obtained during the presentation of 3 plant odors and 3 predator odorants. Odor-responsive neurons in BPA-exposed rats showed greater activity in response to fox odor than did those in control rats. This finding complements the results of our previous behavioral study in which BPA-exposed rats exhibited enhanced avoidance behavior in response to fox odor. Given the close relationship between olfactory signaling and the stress response system, we suspect that BPA modifies the olfactory pathway at the level of the medial amygdala and thus modulates the corresponding stress response.

The use of olfactory testing when diagnosing Parkinson's disease - a systematic review.

INTRODUCTION: The diagnosis of Parkinson's disease (PD) is typically based on the presence of motor symptoms, but in the early phase of the disease, the diagnostic process can be challenging. Examination of non-motor symptoms in patients suspected of PD has gained growing attention. Olfactory tests have shown promising results as ancillary diagnostic tests. The aim of this study was to investigate how olfactory tests may be used clinically in diagnostic process in PD. METHODS: A systematic search was conducted in PubMed for relevant literature on 8 March 2017. A total of 358 articles were found. Our screening process left 27 articles, which were included for further analysis. RESULTS: In all, 20 of the included studies analysed the diagnostic value of olfactory testing by comparing patients with PD to healthy controls. Sensitivities varied from 61% to 95% and specificities from 66% to 99%. Ten studies used olfactory tests to distinguish between PD and diseases that mimic PD. The sensitivities varied from 62% to 92% and the specificities from 65% and 96%. CONCLUSIONS: Olfactory test can be a valuable ancillary tool in the diagnostic process in PD. In a clinical setting, the identification part from Sniffin' Sticks 16 is the most usable because it may be conducted quickly and independently of disease duration and severity. Before using an olfactory test in a clinical setting, it is necessary to adjust the odours to the patient population, and to establish the optimal specificity-adjusted cut-off.

Evaluation of idiopathic olfactory loss with chemosensory event-related potentials and magnetic resonance imaging.

BACKGROUND: Idiopathic olfactory loss (IOL) accounts for a sizable fraction of olfactory dysfunction, but very little is known about its etiology and electrophysiological changes in the olfactory pathway. METHODS: We analyzed the physiology of IOL using chemosensory event-related potentials (ERPs) (olfactory and trigeminal: oERP and tERP) and olfactory pathway magnetic resonance imaging (MRI) measured in adult patients with IOL and healthy controls. Subjective olfactory function was measured by Toyota and Takagi (T&T) olfactometry and Sniffin' Sticks (SS). RESULTS: Olfactory function was worse in patients with IOL compared to controls (T&T, p < 0.001; SS, p < 0.001). oERPs could be evoked in 17 IOL patients. Signals in these patients showed lower amplitude in the N1 and P2 waves than controls (p < 0.05 for both), but there were no difference in latency between the 2 groups (p > 0.05). tERP were detected in all patients and controls; there were no differences in latency and nor amplitude between the 2 groups (p > 0.05). The olfactory bulb (OB) volume was significantly smaller in the IOL group than controls (p < 0.001), but there was no difference in the olfactory sulcus depth between groups (p > 0.05). Better olfactory function was associated with increasing magnitude of N1 amplitude in oERPs (p < 0.05) and increasing OB volume (p < 0.05). CONCLUSION: IOL patients show neurophysiologic deficits and some anatomic differences compared to healthy controls.

Severity of olfactory deficits is reflected in functional brain networks-An fMRI study.

Even though deficits in olfactory function affect a considerable part of the population, the neuronal basis of olfactory deficits remains scarcely investigated. To achieve a better understanding of how smell loss affects neural activation patterns and functional networks, we set out to investigate patients with olfactory dysfunction using functional magnetic resonance imaging (fMRI) and olfactory stimulation. We used patients' scores on a standardized olfactory test as continuous measure of olfactory function. 48 patients (mean olfactory threshold discrimination identification (TDI) score = 16.33, SD = 6.4, range 6 - 28.5) were investigated. Overall, patients showed piriform cortex activation during odor stimulation compared to pure sniffing. Group independent component analysis indicated that the recruitment of three networks during odor stimulation was correlated with olfactory function: a sensory processing network (including regions such as insula, thalamus and piriform cortex), a cerebellar network and an occipital network. Interestingly, recruitment of these networks during pure sniffing was related to olfactory function as well. Our results support previous findings that sniffing alone can activate olfactory regions. Extending this, we found that the severity of olfactory deficits is related to the extent to which neural networks are recruited both during olfactory stimulation and pure sniffing. This indicates that olfactory deficits are not only reflected in changes in specific olfactory areas but also in the recruitment of occipital and cerebellar networks. These findings pave the way for future investigations on whether characteristics of these networks might be of use for the prediction of disease prognosis or of treatment success.

Electrophysiology of Olfactory and Optic Nerve in Outpatient and Intraoperative Settings.

Evoked potentials are time-locked electrophysiologic potentials recorded in response to standardized stimuli using scalp electrodes. These responses provide good temporal resolution and have been used in various clinical and intraoperative settings. Olfactory evoked potentials (OEPs) may be used as an adjunct tool in identifying patients of Parkinson disease and Alzheimer dementia. In clinical practice, visual evoked potentials (VEPs) are particularly useful in identifying subclinical cases of optic neuritis and in treatment surveillance. In recent times, pattern electroretinograms and photopic negative response have been gaining attention in identifying glaucoma suspects. During surgical manipulation, there is a risk of damage to optic or olfactory nerve. Intraoperative neurophysiologic monitoring can provide information regarding the integrity of olfactory or visual pathway. OEPs and VEPs, however, show high degree of variability and are not reliable tools because the responses are extremely susceptible to volatile anesthetic agents. Newer techniques that could possibly circumvent these drawbacks have been developed but are not used extensively. In this article, we briefly review the available techniques to obtain OEPs and VEPs, diagnostic applications, the utility of intraoperative monitoring, the limitations of the current techniques, and the future directions for research.

Activity-Dependent Dysfunction in Visual and Olfactory Sensory Systems in Mouse Models of Down Syndrome.

Activity-dependent synaptic plasticity plays a critical role in the refinement of circuitry during postnatal development and may be disrupted in conditions that cause intellectual disability, such as Down syndrome (DS). To test this hypothesis, visual cortical plasticity was assessed in Ts65Dn mice that harbor a chromosomal duplication syntenic to human chromosome 21q. We find that Ts65Dn mice demonstrate a defect in ocular dominance plasticity (ODP) following monocular deprivation. This phenotype is similar to that of transgenic mice that express amyloid precursor protein (APP), which is duplicated in DS and in Ts65DN mice; however, normalizing APP gene copy number in Ts65Dn mice fails to rescue plasticity. Ts1Rhr mice harbor a duplication of the telomeric third of the Ts65Dn-duplicated sequence and demonstrate the same ODP defect, suggesting a gene or genes sufficient to drive the phenotype are located in that smaller duplication. In addition, we find that Ts65Dn mice demonstrate an abnormality in olfactory system connectivity, a defect in the refinement of connections to second-order neurons in the olfactory bulb. Ts1Rhr mice do not demonstrate a defect in glomerular refinement, suggesting that distinct genes or sets of genes underlie visual and olfactory system phenotypes. Importantly, these data suggest that developmental plasticity and connectivity are impaired in sensory systems in DS model mice, that such defects may contribute to functional impairment in DS, and that these phenotypes, present in male and female mice, provide novel means for examining the genetic and molecular bases for neurodevelopmental impairment in model mice in vivoSIGNIFICANCE STATEMENT Our understanding of the basis for intellectual impairment in Down syndrome is hindered by the large number of genes duplicated in Trisomy 21 and a lack of understanding of the effect of disease pathology on the function of neural circuits in vivo This work describes early postnatal developmental abnormalities in visual and olfactory sensory systems in Down syndrome model mice, which provide insight into defects in the function of neural circuits in vivo and provide an approach for exploring the genetic and molecular basis for impairment in the disease. In addition, these findings raise the possibility that basic dysfunction in primary sensory circuitry may illustrate mechanisms important for global learning and cognitive impairment in Down syndrome patients.

Olfactory dysfunction in early Parkinson's disease is associated with short latency afferent inhibition reflecting central cholinergic dysfunction.

OBJECTIVE: Our study aimed to determine whether the short latency afferent inhibition (SAI) response could be associated with the severity of olfactory dysfunction in PD patients. METHODS: A total of 71 PD patients and 20 controls were enrolled. All PD patients were classified into 3 groups by the severity of the olfactory deficit. Single-pulse transmagnetic stimulation (TMS) parameters and SAI were assessed. RESULTS: The integrated SAI in the PD with anosmia and PD with hyposomia groups was significantly less inhibited than that in the PD with normosmia and control groups [64.79 {Interquartile range (IQR): 59.96, 71.33}, 84.79 {IQR: 75.03, 90.63} versus 36.72 {IQR: 32.28, 48.33}, 42.15 {IQR: 34.60, 44.96}, respectively]. In PD subjects, the severity of olfactory dysfunction also showed a significant negative correlation with the SAI response (r=-0.829, p<0.001). CONCLUSIONS: Considering that the SAI response partly reflects central cholinergic dysfunction and that our study shows a relationship between the SAI response and the severity of olfactory dysfunction in PD, our findings indicate that cholinergic dysfunction could possibly contribute to the pathogenesis of olfactory dysfunction in early PD. SIGNIFICANCE: SAI could be a useful marker to detect severe olfactory dysfunction in PD.

Olfactory disturbances in ageing with and without dementia: towards new diagnostic tools.

BACKGROUND: Olfactory disorders increase with age and often affect elderly people who have pre-dementia or dementia. Despite the frequent occurrence of olfactory changes at the early stages of neurodegenerative disorders such as Alzheimer's disease, olfactory disorders are rarely assessed in daily clinical practice, mainly due to a lack of standardised assessment tools. The aims of this review were to (1) summarise the existing literature on olfactory disorders in ageing populations and patients with neurodegenerative disorders; (2) present the strengths and weaknesses of current olfactory disorder assessment tools; and (3) discuss the benefits of developing specific olfactory tests for neurodegenerative diseases. METHODS: A systematic review was performed of literature published between 2000 and 2015 addressing olfactory disorders in elderly people with or without Alzheimer's disease or other related disorders to identify the main tools currently used for olfactory disorder assessment. RESULTS: Olfactory disorder assessment is a promising method for improving both the early and differential diagnosis of Alzheimer's disease. However, the current lack of consensus on which tests should be used does not permit the consistent integration of olfactory disorder assessment into clinical settings. CONCLUSION: Otolaryngologists are encouraged to use olfactory tests in older adults to help predict the development of neurodegenerative diseases. Olfactory tests should be specifically adapted to assess olfactory disorders in Alzheimer's disease patients.

Nasal neuron PET imaging quantifies neuron generation and degeneration.

Olfactory dysfunction is broadly associated with neurodevelopmental and neurodegenerative diseases and predicts increased mortality rates in healthy individuals. Conventional measurements of olfactory health assess odor processing pathways within the brain and provide a limited understanding of primary odor detection. Quantification of the olfactory sensory neurons (OSNs), which detect odors within the nasal cavity, would provide insight into the etiology of olfactory dysfunction associated with disease and mortality. Notably, OSNs are continually replenished by adult neurogenesis in mammals, including humans, so OSN measurements are primed to provide specialized insights into neurological disease. Here, we have evaluated a PET radiotracer, [11C]GV1-57, that specifically binds mature OSNs and quantifies the mature OSN population in vivo. [11C]GV1-57 monitored native OSN population dynamics in rodents, detecting OSN generation during postnatal development and aging-associated neurodegeneration. [11C]GV1-57 additionally measured rates of neuron regeneration after acute injury and early-stage OSN deficits in a rodent tauopathy model of neurodegenerative disease. Preliminary assessment in nonhuman primates suggested maintained uptake and saturable binding of [18F]GV1-57 in primate nasal epithelium, supporting its translational potential. Future applications for GV1-57 include monitoring additional diseases or conditions associated with olfactory dysregulation, including cognitive decline, as well as monitoring effects of neuroregenerative or neuroprotective therapeutics.

Morphological analysis of regenerated bulbar fibers in relation to neonatal olfaction.

It was revealed that regeneration of the lateral olfactory tract (LOT) occurred in developing rats and the regenerated olfactory system was functional 4 weeks after transection. The aim of this study was to determine the earliest onset of functional recovery in LOT-injured rats and to quantify regenerated nerve components with functional correlation. Neonatal rats on postnatal day (P) 2 were subjected to unilateral transection of the left LOT and underwent unilateral removal of the right olfactory bulb on P11. Functional recovery of the tract injury was assessed by the suckling capability, which can be achieved by olfaction. Suckling capability was observed on P12 in most neonatally LOT-transected pups. Rat pups were subjected to unilateral transection of the left LOT on P2, and received injections of biotinylated dextran amine (BDA) into the bilateral olfactory bulb on P5 to quantify normal and regenerated nerve components in the olfactory cortices at the level of the olfactory tubercle. BDA(+) areas and density indices of the olfactory cortices in the neonatally LOT-transected P12 pups were 11.05×105µm2 and 0.35 on the normal right side and 4.34×105µm2 and 0.21 on the transected left side. We concluded that functional recovery of the LOT-transected neonatal rats occurred as early as 10days after tract transection and that areas and densities of regenerated nerve components essential for functional recovery were approximately 40% and 60% of the age-matched normal values in the olfactory cortices at the level of the olfactory tubercle.

Back on the scent: the olfactory system in CNS demyelinating diseases.

Olfactory dysfunction is recognised across an ever broadening spectrum of neuropsychiatric conditions including central nervous system (CNS) demyelinating diseases such as multiple sclerosis (MS) and neuromyelitis optica (NMO). In this review, we unravel the striking evidence highlighting how olfactory loss is a common clinical feature in MS and NMO. We provide an overview of the supportive psychophysical, electrophysiological, radiological and pathological data that point to the anatomical substrate of olfactory deficits in these diseases. The pattern of underlying pathology affecting the olfactory system is shown to be complex, involving multiple structures that are affected in different ways throughout the course of the disease. This review is the first to synthesise the expanding body of literature on the topic, provides novel insight into the way in which the olfactory system is affected in CNS demyelinating diseases, and raises intriguing questions about the role of this system in the pathogenesis of these diseases.

Olfactory processing in adults with autism spectrum disorders.

BACKGROUND: As evidenced in the DSM-V, autism spectrum disorders (ASD) are often characterized by atypical sensory behavior (hyper- or hypo-reactivity), but very few studies have evaluated olfactory abilities in individuals with ASD. METHODS: Fifteen adults with ASD and 15 typically developing participants underwent olfactory tests focused on superficial (suprathreshold detection task), perceptual (intensity and pleasantness judgment tasks), and semantic (identification task) odor processing. RESULTS: In terms of suprathreshold detection performance, decreased discrimination scores and increased bias scores were observed in the ASD group. Furthermore, the participants with ASD exhibited increased intensity judgment scores and impaired scores for pleasantness judgments of unpleasant odorants. Decreased identification performance was also observed in the participants with ASD compared with the typically developing participants. This decrease was partly attributed to a higher number of near misses (a category close to veridical labels) among the participants with ASD than was observed among the typically developing participants. CONCLUSIONS: The changes in discrimination and bias scores were the result of a high number of false alarms among the participants with ASD, which suggests the adoption of a liberal attitude in their responses. Atypical intensity and pleasantness ratings were associated with hyperresponsiveness and flattened emotional reactions, respectively, which are typical of participants with ASD. The high number of near misses as non-veridical labels suggested that categorical processing is functional in individuals with ASD and could be explained by attention-deficit/hyperactivity disorder. These findings are discussed in terms of dysfunction of the olfactory system.

Involvement of Subcortical Brain Structures During Olfactory Stimulation in Multiple Chemical Sensitivity.

Multiple chemical sensitivity (MCS) patients usually react to odour compounds and the majority of neuroimaging studies assessed, especially at the cortical level, many olfactory-related correlates. The purpose of the present study was to depict sub-cortical metabolic changes during a neutral (NC) and pure (OC) olfactory stimulation by using a recently validated (18)F-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computer tomography procedure in 26 MCS and 11 healthy (HC) resting subjects undergoing a battery of clinical tests. Twelve subcortical volumes of interest were identified by the automated anatomical labeling library and normalized to thalamus FDG uptake. In both groups, when comparing OC to NC, the within-subjects ANOVA demonstrated a relative decreased metabolism in bilateral putamen and hippocampus and a relative increased metabolism in bilateral amygdala, olfactory cortex (OLF), caudate and pallidum. The between-groups ANOVA demonstrated in MCS a significant higher metabolism in bilateral OLF during NC. As in HC subjects negative correlations were found in OC between FDG uptake in bilateral amygdala and hippocampus and odor pleasantness scale, the latter positively correlated with MCS subjects' bilateral putamen FDG uptake in OC. Besides FDG uptake resemblances in both groups were found, for the first time a relative higher metabolism increase in OLF in MCS subjects at rest with respect to HC was found. When merging this aspect to the different subcortical FDG uptake correlations patterns in the two groups, the present study demonstrated to describe a peculiar metabolic index of behavioral and neurological aspects of MCS complaints.