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Brain and Behavior May 2021Pathological abnormalities first appear in the medial temporal regions including entorhinal cortex and parahippocampus in patients with Alzheimer's disease. Previous...
INTRODUCTION
Pathological abnormalities first appear in the medial temporal regions including entorhinal cortex and parahippocampus in patients with Alzheimer's disease. Previous studies showed that olfactory decline in elderly subjects was associated with volume reductions in the left hippocampus and left parahippocampus without cognitive impairment. The aim of this study is to investigate the link between olfaction and volume reductions in the medial temporal regions including the parahippocampus, entorhinal cortex, and hippocampal subfields.
METHOD
27 elderly subjects and 27 young controls were measured olfaction acuity, cognitive function, and structural magnetic resonance imaging. Image processing and gray matter volumetric segmentation were performed with FreeSurfer. Volume data were analyzed with SPSS Statistics software.
RESULTS
Interesting results of this study were that volume reduction in the entorhinal cortex was not directly linked with declining olfactory ability. Volume reduction in the left entorhinal cortex was correlated with volume reduction in the left parahippocampus and dentate gyrus. However, left parahippocampus volume reduction had the greatest impact on olfactory decline, and the entorhinal cortex and dentate gyrus might additionally contribute to olfactory decline.
CONCLUSION
Our results indicate that olfactory decline may be directly reflected in the medial temporal regions as reduced parahippocampus volumes, rather than as morphological changes in the entorhinal cortex and hippocampus. The parahippocampus may play an important role in the association between memory retrieval and olfactory identification.
Topics: Aged; Entorhinal Cortex; Hippocampus; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Smell
PubMed: 33769719
DOI: 10.1002/brb3.2115 -
Frontiers in Cellular Neuroscience 2023Translocator protein (TSPO), a 18 kDa protein found in the outer mitochondrial membrane, has historically been associated with the transport of cholesterol in highly... (Review)
Review
Translocator protein (TSPO), a 18 kDa protein found in the outer mitochondrial membrane, has historically been associated with the transport of cholesterol in highly steroidogenic tissues though it is found in all cells throughout the mammalian body. TSPO has also been associated with molecular transport, oxidative stress, apoptosis, and energy metabolism. TSPO levels are typically low in the central nervous system (CNS), but a significant upregulation is observed in activated microglia during neuroinflammation. However, there are also a few specific regions that have been reported to have higher TSPO levels than the rest of the brain under normal conditions. These include the dentate gyrus of the hippocampus, the olfactory bulb, the subventricular zone, the choroid plexus, and the cerebellum. These areas are also all associated with adult neurogenesis, yet there is no explanation of TSPO's function in these cells. Current studies have investigated the role of TSPO in microglia during neuron degeneration, but TSPO's role in the rest of the neuron lifecycle remains to be elucidated. This review aims to discuss the known functions of TSPO and its potential role in the lifecycle of neurons within the CNS.
PubMed: 37416505
DOI: 10.3389/fncel.2023.1210205 -
Brain Sciences Apr 2023Alzheimer's disease (AD) is associated with the abnormal connection of functional networks. Olfactory impairment occurs in early AD; therefore, exploring alterations in...
Alzheimer's disease (AD) is associated with the abnormal connection of functional networks. Olfactory impairment occurs in early AD; therefore, exploring alterations in olfactory-related regions is useful for early AD diagnosis. We combined the graph theory of local brain network topology with olfactory performance to analyze the differences in AD brain network characteristics. A total of 23 patients with AD and 18 normal controls were recruited for resting-state functional magnetic resonance imaging (fMRI), clinical neuropsychological examinations and the University of Pennsylvania Smell Identification Test (UPSIT). Between-group differences in the topological properties of the local network were compared. Pearson correlations were explored based on differential brain regions and olfactory performance. Statistical analysis revealed a correlation of the degree of cognitive impairment with olfactory recognition function. Local node topological properties were significantly altered in many local brain regions in the AD group. The nodal clustering coefficients of the bilateral temporal pole: middle temporal gyrus (TPOmid), degree centrality of the left insula (INS.L), degree centrality of the right middle temporal gyrus (MTG.R), and betweenness centrality of the left middle temporal gyrus (MTG.L) were related to olfactory performance. Alterations in local topological properties combined with the olfactory impairment can allow early identification of abnormal olfactory-related regions, facilitating early AD screening.
PubMed: 37190596
DOI: 10.3390/brainsci13040631 -
NeuroImage Apr 2021The human sense of smell is highly individual and characterized by a strong variability in the perception and evaluation of olfactory stimuli, depending on cultural...
INTRO
The human sense of smell is highly individual and characterized by a strong variability in the perception and evaluation of olfactory stimuli, depending on cultural imprint and current physiological conditions. Since this individual perspective has often been neglected in fMRI studies on olfactory hedonic coding, this study focuses on the neuronal activity and connectivity patterns resulting from subject-specific olfactory stimulation.
METHODS
Thirty-one normosmic participants took part in a fMRI block designed paradigm consisting of three olfactory stimulation sessions. The most pleasant and unpleasant odors were individually specified during a pre-test for each participant and validated in the main experiment. Mean activation and functional connectivity analysis focusing on the right and left piriform cortex were performed for the predefined olfactory regions-of-interest (ROIs) and compared between the three olfactory conditions.
RESULTS
Individual unpleasant olfactory stimulation as compared to pleasant or neutral did not alter mean BOLD activation in the predefined olfactory ROIs but led to a change in connectivity pattern in the right piriform cortex.
CONCLUSION
Our data suggests that the individual pleasantness of odors is not detectable by average BOLD magnitude changes in primary or secondary olfactory brain areas, but reflected in temporal patterns of joint activation that create a network between the right piriform cortex, the left insular cortex, the orbitofrontal cortex, and the precentral gyrus. This network may serve the evolutionary defense mechanism of olfaction by preparing goal-directed action.
Topics: Adolescent; Adult; Brain; Female; Humans; Individuality; Magnetic Resonance Imaging; Male; Nerve Net; Odorants; Olfactory Perception; Oxygen Consumption; Young Adult
PubMed: 33497777
DOI: 10.1016/j.neuroimage.2021.117782 -
Frontiers in Allergy 2022Currently, clinical assessment of olfaction is largely reliant on subjective methods that require patient participation. The objective method for measuring olfaction,...
IMPORTANCE
Currently, clinical assessment of olfaction is largely reliant on subjective methods that require patient participation. The objective method for measuring olfaction, using electroencephalogram (EEG) readings, can be supplemented with the improved temporal resolution of magnetoencephalography (MEG) for olfactory measurement that can delineate cortical and peripheral olfactory loss. MEG provides high temporal and spatial resolution which can enhance our understanding of central olfactory processing compared to using EEG alone.
OBJECTIVE
To determine the feasibility of building an in-house portable olfactory stimulator paired with electrophysiological neuroimaging technique with MEG to assess olfaction in the clinical setting.
DESIGN SETTING AND PARTICIPANTS
This proof-of-concept study utilized a paired MEG-olfactometer paradigm to assess olfaction in three normosmic participants. We used a two-channel olfactory stimulator to deliver odorants according to a programmed stimulus-rest paradigm. Two synthetic odorants: 2% phenethyl alcohol (rose) and 0.5% amyl acetate (banana) were delivered in increasing increments of time followed by periods of rest. Cortical activity was measured a 306-channel MEG system.
MAIN OUTCOMES AND MEASURES
Primary outcome measure was the relative spectral power for each frequency band, which was contrasted between rest and olfactory stimulation.
RESULTS
Compared to rest, olfactory stimulation produced a 40% increase in relative alpha power within the olfactory cortex bilaterally with both odorants. A 25%-30% increase in relative alpha power occurred in the left orbitofrontal cortex and precentral gyrus with phenethyl alcohol stimulation but not amyl acetate.
CONCLUSION AND RELEVANCE
In this proof-of-concept study, we demonstrate the feasibility of olfactory measurement an olfactometer-MEG paradigm. We found that odorant-specific cortical signatures can be identified using this paradigm, setting the basis for further investigation of this system as a prognostic tool for olfactory loss.
PubMed: 36698377
DOI: 10.3389/falgy.2022.1019265 -
Journal of Neurological Surgery. Part... Oct 2021We investigated the effects of vitamin D deficiency in the peripheral and central smell regions by magnetic resonance imaging (MRI). This retrospective study...
We investigated the effects of vitamin D deficiency in the peripheral and central smell regions by magnetic resonance imaging (MRI). This retrospective study included 29 patients (12 males, 17 females) with 25-dihydroxy vitamin D3 [25(OH) D ] deficiency (group 1) and 34 subjects without 25(OH) D deficiency (14 males, 20 females) (group 2). Using cranial MRIs, the peripheral (olfactory bulb [OB] volume and olfactory sulcus [OS] depth) and central (insular gyrus and corpus amygdala) smell regions were evaluated. The OB volume and OS depth values of the 25(OH) D3 deficiency group were significantly lower than those of the control group ( < 0.05). For the central smell regions, the insular gyrus and corpus amygdala areas of the 25(OH) D3 deficiency group were nonsignificantly lower than those in the control group ( > 0.05). There were positive correlations between OB volumes, OS depths, and insular gyrus and corpus amygdala areas bilaterally in the 25(OH) D3 deficiency group separately and in all subjects (groups 1 and 2) ( < 0.05). In the 25(OH) D3 deficiency group, as the 25(OH) D3 values became lower, the insular gyrus area values decreased bilaterally ( < 0.05). In females, the corpus amygdala area values were lower than in males ( < 0.05). Since vitamin D3 deficiency affected the peripheral and central smell regions negatively, we recommend evaluating patients' vitamin D levels as a health policy to prevent vitamin D3 deficiency-related cranial smell region problems. Moreover, sunlight exposure is very important to increase vitamin D levels, and the public should be informed about this topic.
PubMed: 34513566
DOI: 10.1055/s-0040-1722227 -
Scientific Reports Aug 2023We aimed to investigate changes in olfactory bulb volume and brain network in the white matter (WM) in patients with persistent olfactory disfunction (OD) following...
We aimed to investigate changes in olfactory bulb volume and brain network in the white matter (WM) in patients with persistent olfactory disfunction (OD) following COVID-19. A cross-sectional study evaluated 38 participants with OD after mild COVID-19 and 24 controls, including Sniffin' Sticks identification test (SS-16), MoCA, and brain magnetic resonance imaging. Network-Based Statistics (NBS) and graph theoretical analysis were used to explore the WM. The COVID-19 group had reduced olfactory bulb volume compared to controls. In NBS, COVID-19 patients showed increased structural connectivity in a subnetwork comprising parietal brain regions. Regarding global network topological properties, patients exhibited lower global and local efficiency and higher assortativity than controls. Concerning local network topological properties, patients had reduced local efficiency (left lateral orbital gyrus and pallidum), increased clustering (left lateral orbital gyrus), increased nodal strength (right anterior orbital gyrus), and reduced nodal strength (left amygdala). SS-16 test score was negatively correlated with clustering of whole-brain WM in the COVID-19 group. Thus, patients with OD after COVID-19 had relevant WM network dysfunction with increased connectivity in the parietal sensory cortex. Reduced integration and increased segregation are observed within olfactory-related brain areas might be due to compensatory plasticity mechanisms devoted to recovering olfactory function.
Topics: Humans; Diffusion Tensor Imaging; Cross-Sectional Studies; COVID-19; Brain; White Matter; Magnetic Resonance Imaging
PubMed: 37558765
DOI: 10.1038/s41598-023-40115-7 -
The Journal of Neuroscience : the... Dec 2021Neural oscillations can couple networks of brain regions, especially at lower frequencies. The nasal respiratory rhythm, which elicits robust olfactory bulb...
Neural oscillations can couple networks of brain regions, especially at lower frequencies. The nasal respiratory rhythm, which elicits robust olfactory bulb oscillations, has been linked to episodic memory, locomotion, and exploration, along with widespread oscillatory coherence. The piriform cortex is implicated in propagating the olfactory-bulb-driven respiratory rhythm, but this has not been tested explicitly in the context of both hippocampal theta and nasal respiratory rhythm during exploratory behaviors. We investigated systemwide interactions during foraging behavior, which engages respiratory and theta rhythms. Local field potentials from the olfactory bulb, piriform cortex, dentate gyrus, and CA1 of hippocampus, primary visual cortex, and nasal respiration were recorded simultaneously from male rats. We compared interactions among these areas while rats foraged using either visual or olfactory spatial cues. We found high coherence during foraging compared with home cage activity in two frequency bands that matched slow and fast respiratory rates. Piriform cortex and hippocampus maintained strong coupling at theta frequency during periods of slow respiration, whereas other pairs showed coupling only at the fast respiratory frequency. Directional analysis shows that the modality of spatial cues was matched to larger influences in the network by the respective primary sensory area. Respiratory and theta rhythms also coupled to faster oscillations in primary sensory and hippocampal areas. These data provide the first evidence of widespread interactions among nasal respiration, olfactory bulb, piriform cortex, and hippocampus in awake freely moving rats, and support the piriform cortex as an integrator of respiratory and theta activity. Recent studies have shown widespread interactions between the nasally driven respiratory rhythm and neural oscillations in hippocampus and neocortex. With this study, we address how the respiratory rhythm interacts with ongoing slow brain rhythms across olfactory, hippocampal, and visual systems in freely moving rats. Patterns of network connectivity change with behavioral state, with stronger interactions at fast and slow respiratory frequencies during foraging as compared with home cage activity. Routing of interactions between sensory cortices depends on the modality of spatial cues present during foraging. Functional connectivity and cross-frequency coupling analyses suggest strong bidirectional interactions between olfactory and hippocampal systems related to respiration and point to the piriform cortex as a key area for mediating respiratory and theta rhythms.
Topics: Animals; Cues; Exploratory Behavior; Male; Olfactory Perception; Piriform Cortex; Rats; Rats, Long-Evans; Respiratory Physiological Phenomena; Spatial Behavior; Theta Rhythm; Visual Perception
PubMed: 34667070
DOI: 10.1523/JNEUROSCI.0719-21.2021 -
European Journal of Nuclear Medicine... May 2022Hyposmia is a common feature of COVID-19 and Parkinson's disease (PD). As parkinsonism has been reported after COVID-19, a link has been hypothesized between SARS-CoV2...
PURPOSE
Hyposmia is a common feature of COVID-19 and Parkinson's disease (PD). As parkinsonism has been reported after COVID-19, a link has been hypothesized between SARS-CoV2 infection and PD. We aimed to evaluate brain metabolic correlates of isolated persistent hyposmia after mild-to-moderate COVID-19 and to compare them with metabolic signature of hyposmia in drug-naïve PD patients.
METHODS
Forty-four patients who experienced hyposmia after SARS-COV2 infection underwent brain [F]-FDG PET in the first 6 months after recovery. Olfaction was assessed by means of the 16-item "Sniffin' Sticks" test and patients were classified as with or without persistent hyposmia (COVID-hyposmia and COVID-no-hyposmia respectively). Brain [F]-FDG PET of post-COVID subgroups were compared in SPM12. COVID-hyposmia patients were also compared with eighty-two drug-naïve PD patients with hyposmia. Multiple regression analysis was used to identify correlations between olfactory test scores and brain metabolism in patients' subgroups.
RESULTS
COVID-hyposmia patients (n = 21) exhibited significant hypometabolism in the bilateral gyrus rectus and orbitofrontal cortex with respect to COVID-non-hyposmia (n = 23) (p < 0.002) and in middle and superior temporal gyri, medial/middle frontal gyri, and right insula with respect to PD-hyposmia (p < 0.012). With respect to COVID-hyposmia, PD-hyposmia patients showed hypometabolism in inferior/middle occipital gyri and cuneus bilaterally. Olfactory test scores were directly correlated with metabolism in bilateral rectus and medial frontal gyri and in the right middle temporal and anterior cingulate gyri in COVID-hyposmia patients (p < 0.006) and with bilateral cuneus/precuneus and left lateral occipital cortex in PD-hyposmia patients (p < 0.004).
CONCLUSION
Metabolic signature of persistent hyposmia after COVID-19 encompasses cortical regions involved in olfactory perception and does not overlap metabolic correlates of hyposmia in PD.
Topics: Anosmia; COVID-19; Fluorodeoxyglucose F18; Humans; Olfaction Disorders; Parkinson Disease; RNA, Viral; SARS-CoV-2; Smell
PubMed: 34984501
DOI: 10.1007/s00259-021-05666-9 -
The World Journal of Biological... Feb 2023Olfactory dysfunction is reproducibly reported in psychotic disorders, particularly in association with negative symptoms. The superior frontal gyrus (SFG) has been...
OBJECTIVES
Olfactory dysfunction is reproducibly reported in psychotic disorders, particularly in association with negative symptoms. The superior frontal gyrus (SFG) has been frequently studied in patients with psychotic disorders, in particular with their associations with negative symptoms. The relationship between olfactory functions and brain structure has been studied in healthy controls (HCs). Nevertheless, the studies with patients with psychotic disorders are limited. Here we report the olfactory-brain relationship in a first episode psychosis (FEP) cohort through both hypothesis-driven (centred on the SFG) and data-driven approaches.
METHODS
Using data from 88 HCs and 76 FEP patients, we evaluated the correlation between olfactory functions and structural/resting-state functional magnetic resonance imaging (MRI) data.
RESULTS
We found a significant correlation between the left SFG volume and odour discrimination in FEP patients, but not in HCs. We also observed a significant correlation between rs-fMRI connectivity involving the left SFG and odour discrimination in FEP patients, but not in HCs. The data-driven approach didn't observe any significant correlations, possibly due to insufficient statistical power.
CONCLUSION
The left SFG may be a promising brain region in the context of olfactory dysfunction and negative symptoms in FEP.
Topics: Humans; Schizophrenia; Magnetic Resonance Imaging; Psychotic Disorders; Brain; Olfaction Disorders
PubMed: 35678361
DOI: 10.1080/15622975.2022.2082526