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Life (Basel, Switzerland) Dec 2020Data in the literature report that a number of studies have attempted to identify the exact location of the cortical olfaction representation, searching for evidence...
BACKGROUND
Data in the literature report that a number of studies have attempted to identify the exact location of the cortical olfaction representation, searching for evidence suggesting that sniffing odors can initiate a primary activation of the piriform cortex and the insula. Nowadays, due to the SARS-CoV-2 (COVID-19) outbreak, the functional study of the olfactory system could offer a better understanding of the physiopathology of olfactory perception, elucidating better the possible site(s) of damage induced by the COVID-19 infection. The aim of this paper was to evaluate brain maps generated from functional Magnetic Resonance Imaging (fMRI) data, collected from healthy individuals in response to the same olfactory stimulus.
METHODS
A total of 45 healthy volunteers, without history and/or no clinical signs of sinonasal disease and without history and/or presence of olfactory dysfunction underwent fMRI assessment. Subjects were presented with the same odorous stimuli at specific intervals. fMRI generated brain maps were used in the identification of different cortical areas, involved in the stimuli perception.
RESULTS
The fMRI brain maps showed that odorous stimuli activate primarily the left anterior insula (in 35/45 cases or 77.8%). Other activated areas include: the low temporal gyri, the middle and superior temporal gyri, the frontal and piriform cortex, the anterior cingulate gyrus, the parahippocampal gyrus, the temporopolar area, the para-insular area, the subcentral area, the supramarginal gyrus, the occipital cortex and the cerebellum.
CONCLUSIONS
fMRI resulted as a safe and reliable means to study the perception of olfaction in the cortex. The data of this study suggest that the anterior insula is the main stimulated area when olfactory stimuli are present. This area is always activated, despite the hand and nostril dominance.
PubMed: 33375540
DOI: 10.3390/life11010011 -
PloS One 2013Dehydroepiandrosterone (DHEA) is the most abundant neurosteroid synthesized de novo in the central nervous system. We previously reported that stimulation of the sigma-1...
Dehydroepiandrosterone (DHEA) is the most abundant neurosteroid synthesized de novo in the central nervous system. We previously reported that stimulation of the sigma-1 receptor by DHEA improves cognitive function by activating calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase C and extracellular signal-regulated kinase in the hippocampus in olfactory bulbectomized (OBX) mice. Here, we asked whether DHEA enhances neurogenesis in the subgranular zone of the hippocampal dentate gyrus (DG) and improves depressive-like behaviors observed in OBX mice. Chronic treatment with DHEA at 30 or 60 mg/kg p.o. for 14 days significantly improved hippocampal LTP impaired in OBX mice concomitant with increased CaMKII autophosphorylation and GluR1 (Ser-831) phosphorylation in the DG. Chronic DHEA treatment also ameliorated depressive-like behaviors in OBX mice, as assessed by tail suspension and forced swim tests, while a single DHEA treatment had no affect. DHEA treatment also significantly increased the number of BrdU-positive neurons in the subgranular zone of the DG of OBX mice, an increase inhibited by treatment with NE-100, a sigma-1 receptor antagonist. DHEA treatment also significantly increased phosphorylation of Akt (Ser-473), Akt (Ser-308) and ERK in the DG. Furthermore, GSK-3β (Ser-9) phosphorylation increased in the DG of OBX mice possibly accounting for increased neurogenesis through Akt activation. Finally, we confirmed that DHEA treatment of OBX mice increases the number of BrdU-positive neurons co-expressing β-catenin, a downstream GSK-3βtarget. Overall, we conclude that sigma-1 receptor stimulation by DHEA ameliorates OBX-induced depressive-like behaviors by increasing neurogenesis in the DG through activation of the Akt/GSK-3β/β-catenin pathway.
Topics: Animals; Behavior, Animal; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Dehydroepiandrosterone; Dentate Gyrus; Depression; Enzyme Activation; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Long-Term Potentiation; Mice; Neurogenesis; Olfactory Bulb; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptors, sigma; Signal Transduction; Synapses; beta Catenin; Sigma-1 Receptor
PubMed: 23593332
DOI: 10.1371/journal.pone.0060863 -
European Journal of Nuclear Medicine... Aug 2021In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some patients report functional complaints after apparent...
PURPOSE
In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some patients report functional complaints after apparent recovery from COVID-19. This clinical presentation has been referred as "long COVID." We here present a retrospective analysis of F-FDG brain PET of long COVID patients from the same center with a biologically confirmed diagnosis of SARS-CoV-2 infection and persistent functional complaints at least 3 weeks after the initial infection.
METHODS
PET scans of 35 patients with long COVID were compared using whole-brain voxel-based analysis to a local database of 44 healthy subjects controlled for age and sex to characterize cerebral hypometabolism. The individual relevance of this metabolic profile was evaluated to classify patients and healthy subjects. Finally, the PET abnormalities were exploratory compared with the patients' characteristics and functional complaints.
RESULTS
In comparison to healthy subjects, patients with long COVID exhibited bilateral hypometabolism in the bilateral rectal/orbital gyrus, including the olfactory gyrus; the right temporal lobe, including the amygdala and the hippocampus, extending to the right thalamus; the bilateral pons/medulla brainstem; the bilateral cerebellum (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected). These metabolic clusters were highly discriminant to distinguish patients and healthy subjects (100% correct classification). These clusters of hypometabolism were significantly associated with more numerous functional complaints (brainstem and cerebellar clusters), and all associated with the occurrence of certain symptoms (hyposmia/anosmia, memory/cognitive impairment, pain and insomnia) (p < 0.05). In a more preliminary analysis, the metabolism of the frontal cluster which included the olfactory gyrus was worse in the 7 patients treated by ACE drugs for high blood pressure (p = 0.032), and better in the 3 patients that had used nasal decongestant spray at the infectious stage (p < 0.001).
CONCLUSION
This study demonstrates a profile of brain PET hypometabolism in long COVID patients with biologically confirmed SARS-CoV-2 and persistent functional complaints more than 3 weeks after the initial infection symptoms, involving the olfactory gyrus and connected limbic/paralimbic regions, extended to the brainstem and the cerebellum. These hypometabolisms are associated with patients' symptoms, with a biomarker value to identify and potentially follow these patients. The hypometabolism of the frontal cluster, which included the olfactory gyrus, seems to be linked to ACE drugs in patients with high blood pressure, with also a better metabolism of this olfactory region in patients using nasal decongestant spray, suggesting a possible role of ACE receptors as an olfactory gateway for this neurotropism.
Topics: Brain; COVID-19; Fluorodeoxyglucose F18; Humans; Positron-Emission Tomography; Retrospective Studies; SARS-CoV-2; Post-Acute COVID-19 Syndrome
PubMed: 33501506
DOI: 10.1007/s00259-021-05215-4 -
Microsurgery 2008All surgical approaches to the anterior skull base involve the olfactory cistern and have the risk of damaging the olfactory nerve. The purpose of this study was to...
All surgical approaches to the anterior skull base involve the olfactory cistern and have the risk of damaging the olfactory nerve. The purpose of this study was to describe the microanatomical features of the olfactory cistern and discuss its surgical relevance. In this study, the olfactory cisterns of 15 formalin-fixed adult cadaveric heads were dissected using a surgical microscope. The results showed that the olfactory cistern was situated in the superficial part of the olfactory sulcus, which separated the gyrus retus from the orbital gyrus. In coronal section, the cistern was triangular in shape; its anterior part enveloped the olfactory bulbs and was high and broad; its posterior part was medial-superior to internal carotid artery and was also much broader. There were one or several openings in the inferior wall of the posterior part in 53.4% of the cisterns. The olfactory cistern communicated with the surrounding subarachnoind cisterns through these openings. The middle part of the olfactory cistern gradually narrowed down posteriorly. Most cisterns were spacious with a few fibrous trabeculas and bands between the olfactory nerves and cistern walls. However 23% of the cisterns were narrow with the cistern walls tightly encasing the olfactory nerve. There were two or three of arterial loops in each olfactory sulcus, from which long, fine olfactory arteries originated. The olfactory arteries coursed along the olfactory nerve and gave off many terminal branches to provide the main blood supply to the olfactory nerve in most cisterns, but the blood supply was in segmental style in a few cisterns. Moreover, the veins of the cistern appeared to be more segmental than the olfactory arteries in most cisterns. These results suggested that most olfactory cisterns are spacious with relatively independent blood supply, and it is reasonable to separate the olfactory tract with its independent blood supply from the frontal lobe by 1-2 cm in the subfrontal approach, the pterional approach, or anterior interhemispheric approach. However, in the minority of cases, separation of the olfactory tract is not safe because of the anterior origin of the olfactory arteries or segmental blood supply. It is difficult to separate the olfactory nerve without any damage to the olfactory nerve, even with very skilled hands.
Topics: Adult; Cadaver; Cranial Nerve Injuries; Dissection; Humans; Neurosurgery; Olfactory Nerve
PubMed: 18074374
DOI: 10.1002/micr.20448 -
Frontiers in Neurology 2023To review and analyze the functional connectivity (FC) abnormalities in the brain olfactory network (ON) of patients with chronic rhinosinusitis with olfactory...
OBJECTIVE
To review and analyze the functional connectivity (FC) abnormalities in the brain olfactory network (ON) of patients with chronic rhinosinusitis with olfactory dysfunction (CRSwOD) and explore the relationship between these FC abnormalities and olfactory dysfunction, providing clues to the neurophysiological mechanisms underlying CRSwOD.
METHODS
FC analysis on the ON of patients with CRSwOD and patients with chronic rhinosinusitis without olfactory dysfunction (CRSsOD) identified the regions of the ON with abnormal FC in CRSwOD patients, and the correlation between abnormal FC and clinical scales for chronic rhinosinusitis was analyzed.
RESULTS
(1) Compared with the CRSsOD group, CRSwOD patients showed decreased FC between the bilateral orbitofrontal cortex (OFC) and the right middle frontal gyrus, (2) Receiver operating characteristic (ROC) curve analysis revealed that the FC value between the right middle frontal gyrus and the left OFC (area under the curve (AUC) = 0.852, sensitivity: 0.821, specificity: 0.800, < 0.001) was more capable of distinguishing whether CRS patients may have olfactory dysfunction than the FC value between the right middle frontal gyrus and the right OFC (AUC = 0.827, sensitivity: 0.893, specificity: 0.667, < 0.001), and (3) Lund-Kennedy scores were positively correlated with the FC values between the right middle frontal gyrus and the left OFC ( = 0.443, < 0.018). Lund-Mackay scores were also positively correlated with the FC values between the right middle frontal gyrus and the left OFC ( = 0.468, < 0.012). Questionnaire of Olfactory Disorders-Negative Statements scores were negatively correlated with the FC values between the right middle frontal gyrus and the left OFC ( = -0.481, < 0.001).
CONCLUSION
Persistent nasal inflammation affects the FC between the middle frontal gyrus and the OFC, which may serve as a potential imaging marker for identifying CRSwOD. The severity of nasal inflammation and olfactory damage is closely related to the FC between the middle frontal gyrus and OFC, and the abnormal changes in this FC can be used to explain the neurophysiological mechanisms behind the occurrence of olfactory dysfunction in patients.
PubMed: 38046577
DOI: 10.3389/fneur.2023.1295556 -
Amyotrophic Lateral Sclerosis &... May 2021Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by motor neuron involvement. Although olfactory dysfunction has been...
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by motor neuron involvement. Although olfactory dysfunction has been described in ALS, clinicoradiological features associated with the olfactory dysfunction remain poorly understood. : We enrolled 30 patients with ALS and age- and sex-matched 53 healthy controls (HCs). All participants underwent the odor stick identification test for Japanese (OSIT-J) and clinical assessments, including disease duration, ALSFRS-R, site of onset, forced vital capacity, and cognitive examinations that reflected the general, executive, memory and language function. We investigated the associations between OSIT-J score and clinical features and examined atrophic changes by voxel-based morphometry (VBM) analysis to MRI. : The OSIT-J score was significantly lower in ALS patients than HCs (6.9 ± 3.2 vs. 9.8 ± 1.9, p < 0.001). In ALS, there were significant relationships between OSIT-J score and age at examination, frontal assessment battery, word fluencies, digit span forward, and ADAS-Jcog recognition, but not education, disease type, duration, ALSFRS-R and, %VC. Multiple regression analysis with stepwise method showed the only ADAS-Jcog recognition substantially predicted OSIT-J score. VBM analysis with age, sex, total intracranial volume, and ADAS-Jcog recognition as covariates showed OSIT-J scores were substantially correlated with atrophic changes of left orbital cortex consisting of gyrus rectus and medial orbital gyrus and right hippocampus in ALS. : ALS patients could show substantial olfactory dysfunction in association with orbital cortex and hippocampus involvements. The olfactory examination could be a useful marker for screening of frontotemporal alteration in ALS.
Topics: Adult; Amyotrophic Lateral Sclerosis; Atrophy; Frontal Lobe; Humans; Magnetic Resonance Imaging; Olfaction Disorders
PubMed: 33908332
DOI: 10.1080/21678421.2020.1859544 -
Behavioural Brain Research Apr 1995The presentation of some odorous materials such as xylene or toluene under the snout of rats has been shown to elicit 15-30 Hz fast-wave bursts in both the olfactory...
The presentation of some odorous materials such as xylene or toluene under the snout of rats has been shown to elicit 15-30 Hz fast-wave bursts in both the olfactory bulb and dentate gyrus. Electrical stimulation of the olfactory bulb elicits an evoked potential (latency of first peak is 16-18 ms) in the dentate gyrus. The present study demonstrates that scopolamine or atropine blocks toluene-induced fast-wave bursts in the dentate region and to a lesser degree in the olfactory bulb while leaving dentate gyrus electrically evoked potentials intact. Further, rhythmical burst stimulation of the olfactory bulb at fast-wave frequencies will elicit fast-wave-like oscillations in the dentate gyrus. These fast-wave-like events, unlike evoked potentials to single-pulse stimulation, are abolished after muscarinic receptor antagonism with atropine. Mechanisms at the olfactory bulb and dentate gyrus that produce fast oscillations may involve muscarinic cholinergic synapses while the simple transmission of single, non-oscillatory olfactory signals to the dentate gyrus does not.
Topics: Animals; Electric Stimulation; Electroencephalography; Evoked Potentials; Hippocampus; Male; N-Methylscopolamine; Olfactory Bulb; Parasympatholytics; Rats; Scopolamine; Scopolamine Derivatives; Smell; Stereotaxic Techniques
PubMed: 7619306
DOI: 10.1016/0166-4328(94)00160-h -
Brain Sciences Jul 2022The present study aimed to investigate the association between the functional connectivity (FC) of the olfactory cortex and olfactory performance in Parkinson's disease...
The present study aimed to investigate the association between the functional connectivity (FC) of the olfactory cortex and olfactory performance in Parkinson's disease (PD). Eighty-two early PD patients and twenty-one healthy controls underwent structural and resting-state functional MRI scans, as well as neuropsychological assessments from the Parkinson's Progression Markers Initiative database. A whole brain voxel-wise regression analysis was conducted to evaluate the relationship between the FC of the entorhinal cortex (EC-FC) and olfactory performance. Then, a one-way ANCOVA, based on the regions of interest, was performed with SPSS to investigate the group differences and correlation analysis that were used to analyze the relationships between the FC and neuropsychological assessments. In addition, regression models were used to evaluate the risk factors for the decreased olfactory function. A significantly negative correlation was observed between the olfactory performance and the left EC-FC in the right dorsal cingulate gyrus (dCC) in patients. The PD patients with anosmia exhibited significantly higher FC values than the PD patients with normal olfaction or the PD patients with mild to moderate microsomia. Except for the olfactory performance, no significant correlation was detected between the neuropsychological assessments and the FC values. A linear regression analysis revealed that the increased FC and Geriatric Depression Scale are independently associated with lower the University of Pennsylvania Smell Identification Test scores. The current findings enhanced the understanding of olfactory dysfunction-related pathophysiological mechanisms in early PD and suggested that the left EC-FC in the right dCC may be a potential neuroimaging biomarker for olfactory performance.
PubMed: 35892404
DOI: 10.3390/brainsci12080963 -
Neuroscience Aug 2009Olfactory disorders are common in patients with idiopathic Parkinson's disease (IPD). In IPD patients with hyposmia olfactory event-related potentials (ERPs) are...
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.
Topics: Brain; Brain Mapping; Evoked Potentials; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Olfaction Disorders; Parkinson Disease; Smell
PubMed: 19401224
DOI: 10.1016/j.neuroscience.2009.04.050 -
Cellular and Molecular Life Sciences :... Feb 2013Parkinson's disease (PD), the second most common neurodegenerative disorder, affects 1-2 % of humans aged 60 years and older. The diagnosis of PD is based on motor... (Review)
Review
Parkinson's disease (PD), the second most common neurodegenerative disorder, affects 1-2 % of humans aged 60 years and older. The diagnosis of PD is based on motor symptoms such as bradykinesia, rigidity, tremor, and postural instability associated with the striatal dopaminergic deficit that is linked to neurodegenerative processes in the substantia nigra (SN). In the past, cellular replacement strategies have been evaluated for their potential to alleviate these symptoms. Adult neurogenesis, the generation of new neurons within two proliferative niches in the adult brain, is being intensively studied as one potential mode for cell-based therapies. The subventricular zone provides new neurons for the olfactory bulb functionally contributing to olfaction. The subgranular zone of the hippocampus produces new granule neurons for the dentate gyrus, required for memory formation and proper processing of anxiety provoking stimuli. Recent years have revealed that PD is associated with non-motor symptoms such as hyposmia, anhedonia, lack of novelty seeking behavior, depression, and anxiety that are not directly associated with neurodegenerative processes in the SN. This broad spectrum of non-motor symptoms may partly rely on proper olfactorial processing and hippocampal function. Therefore, it is conceivable that some non-motor deficits in PD are related to defective adult neurogenesis. Accordingly, in animal models and postmortem studies of PD, adult neurogenesis is severely affected, although the exact mechanisms and effects of these changes are not yet fully understood or are under debate due to conflicting results. Here, we review the current concepts related to the dynamic interplay between endogenous cellular plasticity and PD-associated pathology.
Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Disease Models, Animal; Hippocampus; Humans; Neurogenesis; Olfactory Bulb; Parkinson Disease; alpha-Synuclein
PubMed: 22766974
DOI: 10.1007/s00018-012-1062-x