Cerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue.

After contracting COVID-19, a substantial number of individuals develop a Post-COVID-Condition, marked by neurologic symptoms such as cognitive deficits, olfactory dysfunction, and fatigue. Despite this, biomarkers and pathophysiological understandings of this condition remain limited. Employing magnetic resonance imaging, we conduct a comparative analysis of cerebral microstructure among patients with Post-COVID-Condition, healthy controls, and individuals that contracted COVID-19 without long-term symptoms. We reveal widespread alterations in cerebral microstructure, attributed to a shift in volume from neuronal compartments to free fluid, associated with the severity of the initial infection. Correlating these alterations with cognition, olfaction, and fatigue unveils distinct affected networks, which are in close anatomical-functional relationship with the respective symptoms.

Differential connectivity of the posterior piriform cortex in Parkinson's disease and postviral olfactory dysfunction: an fMRI study.

Olfactory dysfunction is a common feature of both postviral upper respiratory tract infections (PV) and idiopathic Parkinson's disease (PD). Our aim was to investigate potential differences in the connectivity of the posterior piriform cortex, a major component of the olfactory cortex, between PV and PD patients. Fifteen healthy controls (median age 66 years, 9 men), 15 PV (median age 63 years, 7 men) and 14 PD patients (median age 70 years, 9 men) were examined with task-based olfactory fMRI, including two odors: peach and fish. fMRI data were analyzed with the co-activation pattern (CAP) toolbox, which allows a dynamic temporal assessment of posterior piriform cortex (PPC) connectivity. CAP analysis revealed 2 distinct brain networks interacting with the PPC. The first network included regions related to emotion recognition and attention, such as the anterior cingulate and the middle frontal gyri. The occurrences of this network were significantly fewer in PD patients compared to healthy controls (p = 0.023), with no significant differences among PV patients and the other groups. The second network revealed a dissociation between the olfactory cortex (piriform and entorhinal cortices), the anterior cingulate gyrus and the middle frontal gyri. This second network was significantly more active during the latter part of the stimulation, across all groups, possibly due to habituation. Our study shows how the PPC interacts with areas that regulate higher order processing and how this network is substantially affected in PD. Our findings also suggest that olfactory habituation is independent of disease.

Impaired olfactory identification in dementia-free individuals is associated with the functional abnormality of the precuneus.

OBJECTIVE: Olfactory dysfunction indicates a higher risk of developing dementia. However, the potential structural and functional changes are still largely unknown. METHODS: A total of 236 participants were enrolled, including 45 Alzheimer's disease (AD) individuals and 191dementia-free individuals. Detailed study methods, comprising neuropsychological assessment and olfactory identification test (University of Pennsylvania smell identification test, UPSIT), as well as structural and functional magnetic resonance imaging (MRI) were applied in this research. The dementia-free individuals were divided into two sub-groups based on olfactory score: dementia-free with olfactory dysfunction (DF-OD) sub-group and dementia-free without olfactory dysfunction (DF-NOD) sub-group. The results were analyzed for subsequent intergroup comparisons and correlations. The cognitive assessment was conducted again three years later. RESULTS: (i) At dementia-free stage, there was a positive correlation between olfactory score and cognitive function. (ii) In dementia-free group, the volume of crucial brain structures involved in olfactory recognition and processing (such as amygdala, entorhinal cortex and basal forebrain volumes) are positively associated with olfactory score. (iii) Compared to the DF-NOD group, the DF-OD group showed a significant reduction in olfactory network (ON) function. (iv) Compared to DF-NOD group, there were significant functional connectivity (FC) decline between PCun_L(R)_4_1 in the precuneus of posterior default mode network (pDMN) and the salience network (SN) in DF-OD group, and the FC values decreased with falling olfactory scores. Moreover, in DF-OD group, the noteworthy reduction in FC were observed between PCun_L(R)_4_1 and amygdala, which was a crucial component of ON. (v) The AD conversion rate of DF-OD was 29.41%, while the DF-NOD group was 12.50%. The structural and functional changes in the precuneus were also observed in AD and were more severe. CONCLUSIONS: In addition to the olfactory circuit, the precuneus is a critical structure in the odor identification process, whose abnormal function underlies the olfactory identification impairment of dementia-free individuals.

Longitudinal brain changes in Parkinson's disease with severe olfactory deficit.

INTRODUCTION: Olfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying neurobiology for this relationship remains unclear but may involve distinct patterns of neurodegeneration. This study aimed to examine longitudinal cortical atrophy and thinning in early-stage PD with severe olfactory deficit (anosmia) without and with concurrent probable RBD. METHODS: Longitudinal MRI data over four years of 134 de novo PD and 49 healthy controls (HC) from the Parkinson Progression Marker Initiative (PPMI) cohort were analyzed using a linear mixed-effects model. Patients were categorized into those with anosmia by the University of Pennsylvania Smell Identification Test (UPSIT) score ≤ 18 (AO+) and those without (UPSIT score > 18, AO-). The AO+ group was further subdivided into AO+ with probable RBD (AO+RBD+) and without (AO+RBD-) for subanalysis. RESULTS: Compared to subjects without baseline anosmia, the AO+ group exhibited greater longitudinal declines in both volume and thickness in the bilateral parahippocampal gyri and right transverse temporal gyrus. Patients with concurrent anosmia and RBD showed more extensive longitudinal declines in cortical volume and thickness, involving additional brain regions including the bilateral precuneus, left inferior temporal gyrus, right paracentral gyrus, and right precentral gyrus. CONCLUSIONS: The atrophy/thinning patterns in early-stage PD with severe olfactory dysfunction include regions that are critical for cognitive function and could provide a structural basis for previously reported associations between severe olfactory deficit and cognitive decline in PD. Concurrent RBD might enhance the dynamics of cortical changes.

Long-term effects of SARS-CoV-2 infection in patients with and without chemosensory disorders at disease onset: a psychophysical and magnetic resonance imaging exploratory study.

A preserved sense of smell and taste allows us to understand many environmental "messages" and results in meaningfully improvements to quality of life. With the COVID-19 pandemic, it became clear how important these senses are for social and nutritional status and catapulted this niche chemosensory research area towards widespread interest. In the current exploratory work, we assessed two groups of post-COVID-19 patients who reported having had (Group 1) or not (Group 2) a smell/taste impairment at the disease onset. The aim was to compare them using validated smell and taste tests as well as with brain magnetic resonance imaging volumetric analysis. Normative data were used for smell scores comparison and a pool of healthy subjects, recruited before the pandemic, served as controls for taste scores. The majority of patients in both groups showed an olfactory impairment, which was more severe in Group 1 (median UPSIT scores: 24.5 Group 1 vs 31.0 Group 2, p = 0.008), particularly among women (p = 0.014). No significant differences emerged comparing taste scores between Group 1 and Group 2, but dysgeusia was only present in Group 1 patients. However, for taste scores, a significant difference was found between Group 1 and controls (p = 0.005). No MRI anatomical abnormalities emerged in any patients while brain volumetric analysis suggested a significant difference among groups for the right caudate nucleus (p = 0.028), although this was not retained following Benjamini-Hochberg correction. This exploratory study could add new information in COVID-19 chemosensory long-lasting impairment and address future investigations on the post-COVID-19 patients' research.

Anterior Skull Base Abnormalities in Congenital Anosmia.

INTRODUCTION: The structures of the skull and the brain are related to each other. Prior work in individuals with isolated congenital anosmia (ICA) showed that these individuals were characterized by olfactory bulb (OB) defects. The aim of this study was to compare the morphological pattern of the anterior skull base surrounding the OB between individuals with ICA and normosmic controls. We meant to investigate whether these features can help distinguish abnormalities from normal variation. METHODS: We conducted a retrospective study to acquire T2-weighted magnetic resonance images from individuals diagnosed with ICA (n = 31) and healthy, normosmic controls matched for age and gender (n = 62). Between both groups, we compared the depth and width of the olfactory fossa, the angle of the ethmoidal fovea, as well as the angle of the lateral lamella of the cribriform plate. Within the ICA group, we further performed subgroup analyses based on the presence or absence of the OB, to investigate whether the morphology of the anterior skull base relates to the presence of OBs. The diagnostic performance of these parameters was evaluated using receiver operating characteristic analysis. RESULTS: Individuals with ICA exhibited a flattened ethmoid roof and shallower olfactory fossa when compared to controls. Further, the absence of the OB was found to be associated with a higher degree of flattening of the ethmoid roof and a shallow olfactory fossa. We reached the results in the following areas under the receiver operating characteristic curves: 0.80 - angle of fovea ethmoidalis, 0.76 - depth of olfactory fossa, 0.70 - angle of lateral lamella of the cribriform plate for significant differentiation between individuals with ICA and normosmic controls. CONCLUSION: Individuals with ICA exhibited an unusual anterior skull base surrounding the OB. This study supports the idea of an integrated development of OB and anterior skull base. Hence, the morphological pattern of the anterior skull base surrounding the OB helps distinguish individuals with ICA from normosmic controls and may therefore be useful for the diagnosis of ICA, although it is certainly not an invariable sign of congenital anosmia.

Can MRI predict olfactory loss and improvement in posttraumatic olfactory dysfunction?

BACKGROUND: Although most patients with post-traumatic olfactory dysfunction (PTOD) undergo MRI, there is no consensus about its diagnostic or prognostic value. The aims were: 1) to classify the extent of post-traumatic neurodegeneration; 2) to determine its relationship with chemosensory dysfunction (smell, taste, trigeminal); and 3) to establish whether MRI can predict olfactory improvement. METHODOLOGY: We conducted a retrospective cohort study based on a series of 56 patients with PTOD. All patients underwent validated psychophysical tests of their smell, taste, and trigeminal functions, otorhinolaryngologic evaluation, and MRI. An experienced radiologist blinded to patient data evaluated 40 chemosensory-relevant brain regions according to a four-point scale (0=no lesion to 3=large lesion). Follow up data after 4 years (on average) were available in 46 patients. RESULTS: The cluster analysis showed 4 brain lesion patterns that differed in lesion localization and severity. They are associated with diagnostic categories: anosmia, hyposmia and normosmia. Two clusters were highly specific for anosmia (100% specificity)and could accurately predict this condition (100% positive predictive value). No clusters were associated with trigeminal or taste dysfunction. Regarding improvement, 72.7% of patients in the cluster with mild lesions experienced subjective and measurable olfactory improvement whereas this was only the case in 21.7-37.5% of patients with larger lesions. The odds of subjective smell improvement were 5.9 times higher in patients within the milder cluster compared to larger ones. CONCLUSIONS: The analysis of brain lesions in PTOD allows corroboration of smell test results and prediction of subjective and measurable improvement.

Olfactory Bulb Volume and Morphology Changes in COVID-19 Patients With Olfactory Disorders Using Magnetic Resonance Imaging.

OBJECTIVES: The aims of the study are to explore the morphological changes of olfactory bulb (OB) and olfactory sulcus in COVID-19 patients with associated olfactory dysfunction (OD) by measuring the OB volume (OBV) and olfactory sulcus depth (OSD) and to compare the measurement values with those of healthy individuals. METHODS: Between March 2020 and January 2022, 31 consecutive hospitalized patients with a diagnosis of COVID-19 with anosmia and hyposmia who underwent brain magnetic resonance imaging and 35 normosmic control individuals were retrospectively included in the study. Bilateral OBV and OSD were measured and shape of the OB was determined based on the consensus by a neuroradiologist and an otorrhynolaryngologist. RESULTS: The mean measurements for the right and the left sides for OBV (38 ± 8.5 and 37.1 ± 8.4, respectively) and OSD (7.4 ± 0.1 and 7.4 ± 1.0 mm, respectively) were significantly lower in COVID-19 patients with OD than those in control group (for the right and the left sides mean OBV 56.3 ± 17.1 and 49.1 ± 13.5, respectively, and mean OSD 9.6 ± 0.8 and 9.4 ± 0.8 mm, respectively). Abnormally shaped OB (lobulated, rectangular, or atrophic) were higher in patient group than those of controls.For the optimal cutoff values, OBV showed sensitivity and specificity values of 90.32% and, 57.14%, for the right, and 87.1% and 62.86% for the left side, respectively (area under the curve, 0.819 and 0.780). Olfactory sulcus depth showed sensitivity and specificity values of 90.32% and 94.29%, for the right, and 96.77% and 85.71%, for the left side, respectively (area under the curve, 0.960 and 0.944). CONCLUSIONS: Decrease in OBV and OSD measurements in COVID-19 patients with OD at the early chronic stage of the disease supports direct damage to olfactory neuronal pathways and may be used to monitor olfactory nerve renewal while returning back to normal function.

Functional magnetic resonance imaging in coronavirus disease 2019 induced olfactory dysfunction.

OBJECTIVE: To evaluate the functional magnetic resonance imaging changes in the olfactory structures of coronavirus disease 2019 patients experiencing olfactory dysfunction. METHODS: This study included patients aged 25-65 years who presented with a sudden loss of smell, confirmed coronavirus disease 2019 infection, and persistent olfactory dysfunction for a minimum of 2 months without any treatment. RESULTS: Irrespective of the side of brain activation, the analysis of the cumulative maximum diameter of the activation zones revealed significantly lower activation in the upper frontal lobe (p = 0.037) and basal ganglia (p = 0.023) in olfactory dysfunction patients. Irrespective of the side of activation, the analysis of the number of activation points demonstrated significantly lower activation in the upper frontal lobe (p = 0.036) and basal ganglia (p = 0.009) in olfactory dysfunction patients. CONCLUSION: Patients with coronavirus-triggered olfactory dysfunction exhibited lower activity in their basal ganglia and upper frontal lobe.

Functional connectivity patterns in parosmia.

OBJECTIVE: Parosmia is a qualitative olfactory dysfunction presenting as "distorted odor perception" in presence of an odor source. Aim of this study was to use resting state functional connectivity to gain more information on the alteration of olfactory processing at the level of the central nervous system level. METHODS: A cross sectional study was performed in 145 patients with parosmia (age range 20-76 years; 90 women). Presence and degree of parosmia was diagnosed on the basis of standardized questionnaires. Participants also received olfactory testing using the "Sniffin' Sticks". Then they underwent resting state scans using a 3 T magnetic resonance imaging scanner while fixating on a cross. RESULTS: Whole brain analyses revealed reduced functional connectivity in salience as well as executive control networks. Region of interest-based analyses also supported reduced functional connectivity measures between primary and secondary olfactory eloquent areas (temporal pole, supramarginal gyrus and right orbitofrontal cortex; dorso-lateral pre-frontal cortex and the right piriform cortex). CONCLUSIONS: Participants with parosmia exhibited a reduced information flow between memory, decision making centers, and primary and secondary olfactory areas.

Hyposmia and apathy in early, de novo Parkinson's disease: Lessons from structural brain connectivity.

INTRODUCTION: The neuroanatomical structures implicated in olfactory and emotional processing overlap significantly. Our understanding of the relationship between hyposmia and apathy, common manifestations of early Parkinson's disease (PD), is inadequate. MATERIALS AND METHODS: We analyzed data on 40 patients with early de-novo idiopathic PD enrolled within 2 years of motor symptom onset in the Parkinson's Progression Markers Initiative (PPMI) study. To be included in the analysis, patients must have smell dysfunction but no apathy at the baseline visit and had completed a diffusion MRI (dMRI) at the baseline visit and at the 48-month follow-up visit. We used the FMRIB Software Library's diffusion tool kit to measure fractional anisotropy (FA) in six regions of interest on dMRI: bilateral anterior corona radiata, left cingulum, left superior corona radiata, genu and body of the corpus callosum. We compared the FA in each region from the dMRI done at the beginning of the study with the follow up studies at 4 years. RESULTS: We found a significant decrease of FA at the bilateral anterior corona radiata, and the genu and body of the corpus callosum comparing baseline scans with follow up images at 4-years after starting the study. CONCLUSION: Structural connectivity changes associated with apathy can be seen early in PD patients with smell dysfunction.

The brain functional connectivity alterations in traumatic patients with olfactory disorder after low-level laser therapy demonstrated by fMRI.

BACKGROUND: Low-level laser therapy (LLLT) has been clinically accepted to accelerate the nerve regeneration process after a nerve injury or transection. We aimed to investigate the neuronal basis and the influence of LLLT on brain functional networks in traumatic patients with olfactory dysfunction. METHODS: Twenty-four Patients with traumatic anosmia/hyposmia were exposed to pleasant olfactory stimuli during a block-designed fMRI session. After a 10-week period, patients as control group and patients who had completed the sessions of LLLT were invited for follow-up testing using the same fMRI protocol. Two-sample t-tests were conducted to explore group differences in activation responding to odorants (p-FDR-corrected <0.05). Differences of functional connectivity were compared between the two groups and the topological features of the olfactory network were calculated. Correlation analysis was performed between graph parameters and TDI score. RESULTS: Compared to controls, laser-treated patients showed increased activation in the cingulate, rectus gyrus, and some parts of the frontal gyrus. Shorter pathlength (p = 0.047) and increased local efficiency (p = 0.043) within the olfactory network, as well as decreased inter-network connectivity within the whole brain were observed in patients after laser surgery. Moreover, higher clustering and local efficiency were related to higher TDI score, as manifested in increased sensitivity to identify odors. CONCLUSIONS: The results support that low-level laser induces neural reorganization process and make new connections in the olfactory structures. Furthermore, the connectivity parameters may serve as potential biomarkers for traumatic anosmia or hyposmia by revealing the underlying neural mechanisms of LLLT.

Peripheric and central olfactory measurements in patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a mental health disorder. PURPOSE: To investigate the peripheric and central olfactory measurements in patients with BD using magnetic resonance imaging (MRI). MATERIAL AND METHODS: This study was conducted retrospectively. Group 1 consisted of 27 euthymic patients with BD (14 men, 13 women) and Group 2 consisted of 27 healthy controls (14 men, 13 women). Olfactory bulb (OB) volume and olfactory sulcus (OS) depth (peripheric), and corpus amygdala and insular gyrus area (central) measurements were performed using cranial MRI. RESULTS: OB volume and OS depth value of the bipolar group were lower than the control group, but there were no significant differences between the groups (P > 0.05). The corpus amygdala and left insular gyrus area of the bipolar group were significantly lower than those in the control group (P < 0.05). There were positive correlations between OB volumes and OS depths, the insular gyrus areas, and the corpus amygdala areas (P < 0.05). As the number of depressive episodes and duration of illness increased in bipolar patients, the depth of the sulcus decreased (P < 0.05). CONCLUSION: In the present study a correlation was detected between OB volumes and the structures, known as emotional processing (e.g. insular gyrus area, corpus amygdala), and clinical features. Accordingly, new treatment techniques, such as olfactory training, may be considered an option in the treatment of such patients with BD.

Cognitive and functional connectivity impairment in post-COVID-19 olfactory dysfunction.

OBJECTIVES: To explore the neuropsychological profile and the integrity of the olfactory network in patients with COVID-19-related persistent olfactory dysfunction (OD). METHODS: Patients with persistent COVID-19-related OD underwent olfactory assessment with Sniffin' Sticks and neuropsychological evaluation. Additionally, both patients and a control group underwent brain MRI, including T1-weighted and resting-state functional MRI (rs-fMRI) sequences on a 3 T scanner. Morphometrical properties were evaluated in olfaction-associated regions; the rs-fMRI data were analysed using graph theory at the whole-brain level and within a standard parcellation of the olfactory functional network. All the MR-derived quantities were compared between the two groups and their correlation with clinical scores in patients were explored. RESULTS: We included 23 patients (mean age 37 ± 14 years, 12 females) with persistent (mean duration 11 ± 5 months, range 2-19 months) COVID-19-related OD (mean score 23.63 ± 5.32/48, hyposmia cut-off: 30.75) and 26 sex- and age-matched healthy controls. Applying population-derived cut-off values, the two cognitive domains mainly impaired were visuospatial memory and executive functions (17 % and 13 % of patients). Brain MRI did not show gross morphological abnormalities. The lateral orbital cortex, hippocampus, and amygdala volumes exhibited a reduction trend in patients, not significant after the correction for multiple comparisons. The olfactory bulb volumes did not differ between patients and controls. Graph analysis of the functional olfactory network showed altered global and local properties in the patients' group (n = 19, 4 excluded due to artifacts) compared to controls. Specifically, we detected a reduction in the global modularity coefficient, positively correlated with hyposmia severity, and an increase of the degree and strength of the right thalamus functional connections, negatively correlated with short-term verbal memory scores. DISCUSSION: Patients with persistent COVID-19-related OD showed an altered olfactory network connectivity correlated with hyposmia severity and neuropsychological performance. No significant morphological alterations were found in patients compared with controls.

Assessment of factors influencing the olfactory bulb volume in patients with post-viral olfactory dysfunction.

PURPOSE: To investigate the factors influencing the volume of the olfactory bulb (OB) in patients with post-viral olfactory dysfunction (PVOD). METHODS: We collected 92 olfactory bulb volumes from patients with PVOD who underwent a sinus computed tomographic and magnetic resonance imaging (MRI) scan of the head and collected clinical information including gender, age, disease course, minimal cross-sectional area, nasal airway resistance, and olfactory function. OB volume was measured in MRI and the scans were evaluated according to the Lund-Mackay (LM) scoring system. RESULTS: Male patients with PVOD had a larger OB volume (ß = 0.284, P < 0.05). OB volume was smaller in patients with a longer course of olfactory dysfunction (ß = - 0.254, P < 0.05). According to the LM scoring system, patients with a higher anterior ethmoidal sinus score had smaller OB volume (ß = - 0.476, P < 0.05). CONCLUSIONS: The study revealed that gender, disease course, and the score of anterior ethmoidal sinusitis can affect the OB volume in patients with PVOD.

The Association Between Depth of the Olfactory Sulcus, Age, Gender and Olfactory Function: An MRI-based Investigation in More Than 1000 Participants.

OBJECTIVE: The present study aimed to investigate the relationship between olfactory sulcus (OS) depth and olfactory function considering age and gender and to provide normative data on OS depth in a population with normal olfactory function. MATERIALS AND METHODS: OS depth was obtained using T1 magnetic resonance imaging scans. Participants (mean age ± sd = 57 ± 16 years, ranging from 20 to 80 years) were screened for olfactory function using the Sniffin' Sticks Screening 12 test. They were divided into an olfactory dysfunction group (n = 604) and a normosmia group (n = 493). Participants also completed questionnaires measuring depression, anxiety and quality of life. RESULTS: The right OS was deeper than the left side in all age groups. On the left side, women had deeper OS compared with men, exhibiting a higher degree of symmetry in left and right OS depth in women. Variance of olfactory function was largely determined by age, OS depth explained only minor portions of this variance. Normative data for minimum OS depth was 7.55 mm on the left and 8.78 mm on the right for participants aged between 18 and 35 years (n = 144), 6.47 mm on the left and 6.99 mm on the right for those aged 36-55 years (n = 120), and 5.28 mm on the left and 6.19 mm on the right for participants older than 55 years (n = 222). CONCLUSION: Considering the limited resolution of the presently used T1 weighted MR scans and the nature of the olfactory screening test, OS depth explained only minor portions of the variance of olfactory function, which was largely determined by age. Age-related normative data of OS depth are presented as a reference for future work.

MRI evidence of olfactory system alterations in patients with COVID-19 and neurological symptoms.

BACKGROUND AND OBJECTIVE: Despite olfactory disorders being among the most common neurological complications of coronavirus disease 2019 (COVID-19), their pathogenesis has not been fully elucidated yet. Brain MR imaging is a consolidated method for evaluating olfactory system's morphological modification, but a few quantitative studies have been published so far. The aim of the study was to provide MRI evidence of olfactory system alterations in patients with COVID-19 and neurological symptoms, including olfactory dysfunction. METHODS: 196 COVID-19 patients (median age: 53 years, 56% females) and 39 controls (median age 55 years, 49% females) were included in this cross-sectional observational study; 78 of the patients reported olfactory loss as the only neurological symptom. MRI processing was performed by ad-hoc semi-automatic processing procedures. Olfactory bulb (OB) volume was measured on T2-weighted MRI based on manual tracing and normalized to the brain volume. Olfactory tract (OT) median signal intensity was quantified on fluid attenuated inversion recovery (FLAIR) sequences, after preliminary intensity normalization. RESULTS: COVID-19 patients showed significantly lower left, right and total OB volumes than controls (p < 0.05). Age-related OB atrophy was found in the control but not in the patient population. No significant difference was found between patients with olfactory disorders and other neurological symptoms. Several outliers with abnormally high OT FLAIR signal intensity were found in the patient group. CONCLUSIONS: Brain MRI findings demonstrated OB damage in COVID-19 patients with neurological complications. Future longitudinal studies are needed to clarify the transient or permanent nature of OB atrophy in COVID-19 pathology.

Brain structural analysis in patients with post-traumatic anosmia: Voxel-based and surface-based morphometry.

PURPOSE AND BACKGROUND: Voxel-based morphometry (VBM) and surfaced-based morphometry (SBM) investigate the characteristics of gray matter (GM) in various diseases such as post-traumatic anosmia (PTA). This study uses SBM and VBM to examine neuroanatomical measurements of GM and its functional correlates in patients with PTA. METHODS: MRI images and olfactory test results were collected from 39 PTA patients and 39 healthy controls. Sniffin' Sticks test was used to assess olfactory function. GM structure was analyzed using CAT12 and FreeSurfer, and olfactory bulb (OB) volume and olfactory sulcus (OS) depth were calculated using 3D-Slicer. RESULTS: Anosmic patients showed lower scores in the Sniffin' Sticks olfactory test, as well as reduction of OB volume and OS depth compared to control subjects. In these patients, overlapping changes were found between the VBM and SBM findings in the areas with significant effects, in particular, orbitofrontal cortex, superior and middle frontal gyrus, superior and middle temporal gyrus, anterior cingulate cortex, and insular cortex. Using SBM, decreased cortical thickness clusters were located in inferior and superior parietal gyrus. Further analysis in the region of interest demonstrated correlations between the orbitofrontal cortex and odor threshold score as well as the middle frontal gyrus and smell loss duration. CONCLUSION: These findings show that the morphological alterations in the OB, OS, and the central olfactory pathways might contribute to the pathogenic mechanism of olfactory dysfunction after head injury.

Structural brain changes in post-acute COVID-19 patients with persistent olfactory dysfunction.

OBJECTIVE: This research aims to study structural brain changes in patients with persistent olfactory dysfunctions after coronavirus disease 2019 (COVID-19). METHODS: COVID-19 patients were evaluated using T1-weighted and diffusion tensor imaging (DTI) on a 3T MRI scanner, 9.94 ± 3.83 months after COVID-19 diagnosis. Gray matter (GM) voxel-based morphometry was performed using FSL-VBM. Voxelwise statistical analysis of the fractional anisotropy, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity was carried out with the tract-based spatial statistics in the olfactory system. The smell identification test (UPSIT) was used to classify patients as normal olfaction or olfactory dysfunction groups. Intergroup comparisons between GM and DTI measures were computed, as well as correlations with the UPSIT scores. RESULTS: Forty-eight COVID-19 patients were included in the study. Twenty-three were classified as olfactory dysfunction, and 25 as normal olfaction. The olfactory dysfunction group had lower GM volume in a cluster involving the left amygdala, insular cortex, parahippocampal gyrus, frontal superior and inferior orbital gyri, gyrus rectus, olfactory cortex, caudate, and putamen. This group also showed higher MD values in the genu of the corpus callosum, the orbitofrontal area, the anterior thalamic radiation, and the forceps minor; and higher RD values in the anterior corona radiata, the genu of the corpus callosum, and uncinate fasciculus compared with the normal olfaction group. The UPSIT scores for the whole sample were negatively associated with both MD and RD values (p-value ≤0.05 FWE-corrected). INTERPRETATION: There is decreased GM volume and increased MD in olfactory-related regions explaining prolonged olfactory deficits in post-acute COVID-19 patients.

Deficits in peripheric and central olfactory measurements in smokers: evaluated by cranial MRI.

OBJECTIVES: Cigarette smoking remains a serious health problem all over the world. We investigated the peripheral and central olfactory pathways in young male smokers to determine whether there is a relationship between the amount of cigarettes smoked and duration of smoking and the dimensions of the olfactory areas. METHODS: In this retrospective study, cranial Magnetic Resonance Imaging (MRI) images of adult male smokers aged ≤ 40 years (n = 51) and 50 healthy male adults were analyzed. The olfactory bulbus (OB) volumes and olfactory sulcus (OS) depths, insular gyrus, and corpus amygdala areas were measured via cranial MRI. In the smoker group, the number of cigarettes smoked and duration of smoking were noted and the Brinkmann index was calculated. RESULTS: OB volume, OS depth, and the insular gyrus areas of the smokers were lower than in the control group (p < 0.05). There were no differences between the groups in terms of the corpus amygdala measurements (p > 0.05). No significant correlations were found between the number of cigarettes smoked daily, smoking duration, and the Brinkmann index and the peripheral and central olfactory measurements in our study (p > 0.05). CONCLUSIONS: In smokers, OB volumes, the OS, and the central areas decrease bilaterally, regardless of smoking duration and number of cigarettes smoked daily. This could be related to inflammatory mediators that may be harmful to the olfactory neuroepithelium, gray matter atrophy in the brain, or endothelial damage related to smoking and its effects on blood support to the brain and olfactory regions.