A characteristic of olfactory function in four types of dementia and non-dementia subjects using smell identification test.

BACKGROUND: For those outpatients who were consulted for memory loss, the Japanese version of University of Pennsylvania Smell Identification Test (UPSIT-J) was performed to examine olfactory function. In the same way, the revised version of Hasegawa Dementia Scale, Mini Mental State Examination, Clinical Dementia Rating and brain magnetic resonance imaging were used to investigate the cognitive function. In the present study, we evaluated the olfactory function of elderly subjects, including those with dementia, by means of UPSIT-J and we examined their characteristics. METHODS: The characteristics of dementia as Alzheimer type group (AD.G), mixed type group (MixD.G), vascular type group (VaD.G), dementia with Lewy bodies group (DLB.G) and the groups which had no dementia as low score group (LS.G), high score group (HS.G), and healthy group (H.G), were examined. RESULTS: The numbers of olfactory discriminating scores (nODS) were significantly lower in all the dementia groups than in all the LS.G, HS.G and the H.G. No significant difference was observed in nODS between AD.G and DLB.G. The rate of nODS with less than five scores were as follows: AD.G (80.1%), MixD.G (91.5%), VaD.G (63.1%), DLB.G (89.6%), LS.G (50.8%), HS.G (18.6%), H.G (15.6%). A significant positive correlation was found between nODS and Hasegawa Dementia Scale and Mini Mental State Examination scores (r = 0.567, r = 0.532, respectively), which was significant negatively correlated for Clinical Dementia Rating (r = -0.578). A significant negative correlation was observed between nODS and Z score of voxel-based specific regional analysis for Z score of Alzheimer's disease (VSRAD) (r = 0.463). CONCLUSION: nODS showed a significant correlation between cognitive function tests and brain atrophy level. These results indicate that UPSIT-J is considered a psycho-physiological index useful for the diagnosis and early detection of dementia.

Olfactory training with four and eight odors: comparison with clinical testing and olfactory bulb volumetrics.

PURPOSE: Post-infectious olfactory dysfunction (PIOD) is one of the most common causes of olfactory impairment but has limited treatment options. Recently, olfactory training (OT) has been considered an effective treatment method; however, several questions have arisen regarding its optimal scheme. The aim of this study was to assess whether an OT scheme with 8 odors is more effective than the classic OT scheme with 4 odors by comparing psychophysical test results and olfactory bulb (OB) volumetrics. METHODS: In this prospective cohort study, 72 patients with PIOD were included. The patients followed either the classic 4-odor OT scheme (COT; n = 34 patients) or an extended 8-odor scheme (EOT; n = 38 patients) for 16 weeks. All patients underwent olfactory testing with a Sniffin'Sticks battery test at 0, 8, and 16 weeks. Of the patients, 38 underwent brain magnetic resonance imaging for OB volumetric assessment before and after treatment. RESULTS: The comparison of the olfactory test results did not show any significant difference between the two study groups, in agreement with the OB volumetrics. The convex OB showed better test results than the non-convex OB, with significantly better improvement after treatment regardless of OT type. The EOT group presented significantly better adherence than the COT group. CONCLUSION: The number of odors did not appear to play a significant role in the effect of the OT. However, the training scheme with more than four odors showed better adherence among the patients in a long-term treatment plan. The shape of the OB may have prognostic value in clinical assessment and warrants further investigation.

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.

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.

Quantitative analysis of the olfactory system in pediatric epilepsy: a magnetic resonance imaging study

PURPOSE: Olfactory dysfunction is a well-known complication in epilepsy. Studies have demonstrated that olfactory bulb volume (OBV), olfactory tract length (OTL), and olfactory sulcus depth (OSD) can be reliably evaluated using magnetic resonance imaging (MRI). In this study, we compared the OBV, OTL, and OSD values of children with epilepsy and those of healthy children (controls) of similar age. Our aim was to determine the presence of olfactory dysfunction in children with epilepsy and demonstrate the effects of the epilepsy type and treatment on olfactory function in these patients. METHODS: Cranial MRI images of 36 patients with epilepsy and 108 controls (3-17 years) were evaluated. The patients with epilepsy were divided into groups according to the type of disease and treatment method. Subsequently, OBV and OSD were measured from the coronal section and OTL from the sagittal section. The OBV, OTL, and OSD values were compared between the epilepsy group, subgroups, and controls. RESULTS: OBV was significantly reduced in the children with epilepsy compared with the control group (P < 0.001). No significant difference between the healthy children and those with epilepsy was determined in terms of OTL and OSD. Although OBV was moderately positively correlated with age in the control group (r = 0.561, P < 0.001), it was poorly correlated with age in children with epilepsy (r = 0.393, P = 0.018). CONCLUSION: The results of our study indicate that OBV decreases in children with epilepsy, but epilepsy type and treatment method do not affect OBV, OTL, or OSD (P > 0.05).

Clinical and Imaging Evaluation of COVID-19-Related Olfactory Dysfunction.

BACKGROUND: Olfactory dysfunction has been reported in 47.85% of COVID patients. It can be broadly categorized into conductive or sensorineural olfactory loss. Conductive loss occurs due to impaired nasal air flow, while sensorineural loss implies dysfunction of the olfactory epithelium or central olfactory pathways. OBJECTIVES: The aim of this study was to analyze the clinical and imaging findings in patients with COVID-related olfactory dysfunction. Additionally, the study aimed to investigate the possible mechanisms of COVID-related olfactory dysfunction. METHODS: The study included 110 patients with post-COVID-19 olfactory dysfunction, and a control group of 50 COVID-negative subjects with normal olfactory function. Endoscopic nasal examination was performed for all participants with special focus on the olfactory cleft. Smell testing was performed for all participants by using a smell diskettes test. Olfactory pathway magnetic resonance imaging (MRI) was done to assess the condition of the olfactory cleft and the dimensions and volume of the olfactory bulb. RESULTS: Olfactory dysfunction was not associated with nasal symptoms in 51.8% of patients. MRI showed significantly increased olfactory bulb dimensions and volume competed to controls. Additionally, it revealed olfactory cleft edema in 57.3% of patients. On the other hand, radiological evidence of sinusitis was detected in only 15.5% of patients. CONCLUSION: The average olfactory bulb volumes were significantly higher in the patients' group compared to the control group, indicating significant edema and swelling in the olfactory bulb in patients with COVID-related olfactory dysfunction. Furthermore, in most patients, no sinonasal symptoms such as nasal congestion or rhinorrhea were reported, and similarly, no radiological evidence of sinusitis was detected. Consequently, the most probable mechanism of COVID-related olfactory dysfunction is sensorineural loss through virus spread and damage to the olfactory epithelium and pathways.

Loss of smelling is an early marker of aging and is associated with inflammation and DNA damage in C57BL/6J mice.

Olfactory dysfunction is a prevalent symptom and an early marker of age-related neurodegenerative diseases in humans, including Alzheimer's and Parkinson's Diseases. However, as olfactory dysfunction is also a common symptom of normal aging, it is important to identify associated behavioral and mechanistic changes that underlie olfactory dysfunction in nonpathological aging. In the present study, we systematically investigated age-related behavioral changes in four specific domains of olfaction and the molecular basis in C57BL/6J mice. Our results showed that selective loss of odor discrimination was the earliest smelling behavioral change with aging, followed by a decline in odor sensitivity and detection while odor habituation remained in old mice. Compared to behavioral changes related with cognitive and motor functions, smelling loss was among the earliest biomarkers of aging. During aging, metabolites related with oxidative stress, osmolytes, and infection became dysregulated in the olfactory bulb, and G protein coupled receptor-related signaling was significantly down regulated in olfactory bulbs of aged mice. Poly ADP-ribosylation levels, protein expression of DNA damage markers, and inflammation increased significantly in the olfactory bulb of older mice. Lower NAD+ levels were also detected. Supplementation of NAD+ through NR in water improved longevity and partially enhanced olfaction in aged mice. Our studies provide mechanistic and biological insights into the olfaction decline during aging and highlight the role of NAD+ for preserving smelling function and general health.

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.

Olfactory system measurements in COVID-19: a systematic review and meta-analysis.

PURPOSE: The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction in COVID-19. We aimed to aggregate the results of the studies which reported imaging of the olfactory system of patients with COVID-19 versus controls. METHODS: PubMed and EMBASE were searched to identify relevant literature reporting the structural imaging characteristics of the olfactory bulb (OB), olfactory cleft, olfactory sulcus (OS), or olfactory tract in COVID-19 patients. Hedge's g and weighted mean difference were used as a measure of effect size. Quality assessment, subgroup analyses, meta-regression, and sensitivity analysis were also conducted. RESULTS: Ten studies were included in the qualitative synthesis, out of which seven studies with 183 cases with COVID-19 and 308 controls without COVID-19 were enrolled in the quantitative synthesis. No significant differences were detected in analyses of right OB volume and left OB volume. Likewise, right OS depth and left OS depth were also not significantly different in COVID-19 cases compared to non-COVID-19 controls. Also, we performed subgroup analysis, meta-regression, and sensitivity analysis to investigate the potential effect of confounding moderators. CONCLUSION: The findings of this review did not confirm alterations in structural imaging of the olfactory system, including OB volume and OS depth by Covid-19 which is consistent with the results of recent histopathological evaluations.

Reconsidering the olfactory and brain structures in Kallmann's syndrome: New findings in the analysis of volumetry.

OBJECTIVE: Kallmann's syndrome (KS) is characterized by hypogonadotropic hypogonadism and olfactory disorders. The complementary exams for evaluating of patients with hypogonadotrophic hypogonadism are important for the diagnosis and management of these patients. PATIENTS: We performed a well-established olfactory Sniffin' Stick test (SST) on 17 adult patients with KS and brain magnetic resonance imaging (MRI) to evaluate olfactory structures and further analysis by Freesurfer, a software for segmentation and volumetric evaluation of brain structures. We compared the Freesurfer results with 34 healthy patients matched for age and sex and performed correlations between the data studied. RESULTS: More than half of the patients with KS reported preserved smell but had olfactory disorders in the SST. In the MRI, 16 patients showed changes in the olfactory groove, the olfactory bulb-tract complex was altered in all of them and 52% had symmetrical structural changes. Interestingly, the pituitary gland was normal in only 29%. Regarding correlations, symmetrical changes in the olfactory structures were related to anosmia in 100%, while asymmetric changes induced anosmia in only 50% (p = .0294). In Freesurfer's assessment, patients with KS, compared to controls, had lower brainstem volume. In those with aplastic anterior olfactory sulcus, the brainstem volume was lower than in hypoplasia (p = .0333). CONCLUSIONS: Olfactory assessment and MRI proved to be important auxiliary tools for the diagnosis and management of patients with KS. New studies are needed to confirm the decrease in brainstem volume found by the Freesurfer software in patients with KS. Further studies are needed to confirm the decrease in brainstem volume found by the Freesurfer software in patients with KS.

Lipopolysaccharide-Initiated Rhinosinusitis Causes Neuroinflammation and Olfactory Dysfunction in Mice.

BACKGROUND: Olfactory dysfunction is a common disease and it may be caused by sinonasal inflammation, toxin inhalation, or neurological disorders. After sinonasal inflammation, if both olfactory neuroinflammation and olfactory dysfunction occur still under investigation. OBJECTIVE: This study aimed to investigate whether neuroinflammation and olfactory dysfunction occur after lipopolysaccharide (LPS)-initiated rhinosinusitis. METHODS: Adult C57BL/6 mice were intranasally administered with LPS for 3 weeks. The olfactory function was evaluated with a buried food test. The inflammatory status of sinonasal cavity and olfactory bulb was evaluated with histology and biochemistry. RESULTS: After 3-week LPS treatment, mice developed olfactory dysfunction, sinonasal cavity, and olfactory bulb inflammation. LPS-treated mice had greater sinonasal mucosal thickness. Besides, pro-inflammatory interleukin-6, the number of goblet cells and neutrophils in the sinonasal cavity was increased after LPS administration. The olfactory sensory neurons in the olfactory epithelium and the olfactory bulb were decreased, and the olfactory function was impaired by LPS administration. Inflammatory cytokines such as interferon-γ and tumor necrosis factor-α were increased in the olfactory bulb. CONCLUSION: This study showed that LPS-initiated rhinosinusitis caused olfactory neuroinflammation and olfactory dysfunction in mice.

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.

Mesoporous silica nanoparticle-encapsulated Bifidobacterium attenuates brain Aß burden and improves olfactory dysfunction of APP/PS1 mice by nasal delivery.

BACKGROUND: Dysbiosis or imbalance of gut microbiota in Alzheimer's disease (AD) affects the production of short-chain fatty acids (SCFAs), whereas exogenous SCFAs supplementation exacerbates brain Aß burden in APP/PS1 mice. Bifidobacterium is the main producer of SCFAs in the gut flora, but oral administration of Bifidobacterium is ineffective due to strong acids and bile salts in the gastrointestinal tract. Therefore, regulating the levels of SCFAs in the gut is of great significance for AD treatment. METHODS: We investigated the feasibility of intranasal delivery of MSNs-Bifidobacterium (MSNs-Bi) to the gut and their effect on behavior and brain pathology in APP/PS1 mice. RESULTS: Mesoporous silica nanospheres (MSNs) were efficiently immobilized on the surface of Bifidobacterium. After intranasal administration, fluorescence imaging of MSNs-Bi in the abdominal cavity and gastrointestinal tract revealed that intranasally delivered MSNs-Bi could be transported through the brain to the peripheral intestine. Intranasal administration of MSNs-Bi not only inhibited intestinal inflammation and reduced brain Aß burden but also improved olfactory sensitivity in APP/PS1 mice. CONCLUSIONS: These findings suggested that restoring the balance of the gut microbiome contributes to ameliorating cognitive impairment in AD, and that intranasal administration of MSNs-Bi may be an effective therapeutic strategy for the prevention of AD and intestinal disease.

Neuronal network-based biomimetic chip for long-term detection of olfactory dysfunction model in early-stage Alzheimer's disease.

Olfactory dysfunction is an early symptom of neurodegenerative disease. Amyloid-beta oligomers (AßOs), the pathologic protein of Alzheimer's disease (AD), have been confirmed to be firstly deposited in olfactory bulb (OB), causing smell to malfunction. However, the detailed mechanisms underlying pathogenic nature of AßOs-induced olfactory neuronal degeneration in AD are not completely realized. Here, an early-stage olfactory dysfunction pathological model of AD in vitro based on biomimetic OB neuronal network chip was established for dynamic multi-site detection of neuronal electrical activity and network connection. We found both spike firing and correlation of overall neuronal network change regularly displayed gradually active state and then rapidly decay state after AßOs induction. Moreover, MK-801 and memantine were administrated at early-stage to detect alteration of OB neurons simulating nasal administration for AD treatment, which showed an almost recovery through the intermittent firing pattern. Together, this neuronal network-on-chip has revealed synaptic impairment and network neurodegeneration of olfactory dysfunction in AD, providing potential mechanisms information for early-stage progressive olfactory amyloidogenic pathology.

Olfactory Bulb Integrity in Frontotemporal Dementia and Alzheimer's Disease.

BACKGROUND: Olfactory dysfunction is highly prevalent in dementia syndromes, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). The structural integrity of the olfactory bulb (OB) is thought to play a critical role in odor detection and identification, but no MRI study has measured OB volume in FTD, or measured OB volume longitudinally in AD. OBJECTIVE: To measure OB volume in FTD and AD patients longitudinally using MRI. METHODS: This study measured OB volumes using MRI in patients diagnosed with behavioral-variant FTD (n = 55), semantic dementia (n = 34), progressive non-fluent aphasia (n = 30), AD (n = 50), and healthy age-matched controls (n = 55) at their first visit to a dementia research clinic ('baseline'). Imaging data in patients 12-months later were analyzed where available (n = 84) for longitudinal assessment. Volumes of subcortical and cortical olfactory regions ('olfactory network') were obtained via surface-based morphometry. RESULTS: Results revealed that in AD and FTD at baseline, OB volumes were similar to controls, whereas volumes of olfactory network regions were significantly reduced in all patient groups except in progressive non-fluent aphasia. Longitudinal data revealed that OB volume became significantly reduced (10-25% volume reduction) in all dementia groups with disease progression. CONCLUSION: Olfactory dysfunction is common in patients diagnosed with AD or FTD, but our results indicate that there is no detectable volume loss to the OBs upon first presentation to the clinic. Our findings indicate that the OBs become detectably atrophied later in the disease process. OB atrophy indicates the potential usefulness for OBs to be targeted in interventions to improve olfactory function.

Analysis of conductive olfactory dysfunction using computational fluid dynamics.

Conductive olfactory dysfunction (COD) is caused by an obstruction in the nasal cavity and is characterized by changeable olfaction. COD can occur even when the olfactory cleft is anatomically normal, and therefore, the cause in these cases remains unclear. Herein, we used computational fluid dynamics to examine olfactory cleft airflow with a retrospective cohort study utilizing the cone beam computed tomography scan data of COD patients. By measuring nasal-nasopharynx pressure at maximum flow, we established a cut-off value at which nasal breathing can be differentiated from combined mouth breathing in COD patients. We found that increased nasal resistance led to mouth breathing and that the velocity and flow rate in the olfactory cleft at maximum flow were significantly reduced in COD patients with nasal breathing only compared to healthy olfactory subjects. In addition, we performed a detailed analysis of common morphological abnormalities associated with concha bullosa. Our study provides novel insights into the causes of COD, and therefore, it has important implications for surgical planning of COD, sleep apnea research, assessment of adenoid hyperplasia in children, and sports respiratory physiology.

Effect of olfactory bulb atrophy on the success of olfactory training.

PURPOSE: To evaluate the success of olfactory training in patients with olfactory loss and olfactory bulb (OB) atrophy detected on magnetic resonance imaging (MRI) and other characteristics. METHODS: This study included 48 patients with olfactory loss who underwent a nasal endoscopic examination and MRI before olfactory training. The Korean Version of the Sniffin' Sticks Test was performed before and after training. The olfactory training success was defined as an improvement of more than 6 points in the Threshold-Discrimination-Identification (TDI) score. Patient characteristics and OB atrophy pre-training were compared between successful and unsuccessful groups. RESULTS: The etiology of olfactory loss included respiratory viral infection in 30 (62.5%), trauma in 10 (20.8%), and idiopathic loss in 8 (16.7%) patients. Twenty-three (47.9%) of 48 patients exhibited successful olfactory training. Etiology, age, gender, and symptom duration were not different between unsuccessful and successful groups. Pre-training discrimination, identification, and TDI scores were significantly different between unsuccessful and successful groups (P < 0.05). Success rate of patients with bilateral OB atrophy was significantly lower than that of patients with unilateral OB atrophy and normal morphology (P = 0.006). OB height was significantly lower in the unsuccessful group than in the successful group (P < 0.05). Bilateral OB atrophy was an independent risk factor for failure of olfactory training according to the multivariate analysis. CONCLUSION: Olfactory loss patients with bilateral OB atrophy may not be able to improve olfactory function after olfactory training.

Reorganizing brain structure through olfactory training in post-traumatic smell impairment: An MRI study.

PURPOSE AND BACKGROUND: Post-traumatic olfactory dysfunction (PTOD), mostly caused by head injury, is thought to be associated with changes in the structure and function of the brain olfactory processing areas. Training and repeated exposure to odorants lead to enhanced olfactory capability. This study investigated the effects of a 16-weeks olfactory training (OT) on olfactory function and brain structure. METHODS: Twenty-five patients with PTOD were randomly divided in three groups: (1) 9 control patients who did not receive any training, (2) 9 patients underwent classical OT by 4 fixed odors, and (3) 7 patients underwent modified OT coming across 4 sets of 4 different odors sequentially. Before and after the training period, all patients performed olfactory function tests and structural magnetic resonance imaging (MRI). Sniffin' Sticks test was used to assess olfactory function. MRI data were analyzed using voxel-based morphometry and surface-based morphometry. RESULTS: Both trained groups showed a considerable recovery of olfactory function, especially in odor identification. MRI data analysis revealed that the classical OT leads to increases in cortical thickness/density of several brain regions, including the right superior and middle frontal gyrus, and bilateral cerebellums. In addition, the modified OT yielded a lower extent of cortical measures in the right orbital frontal cortex and right insular. Following modified OT, a positive correlation was observed between the odor identification and the right orbital frontal cortex. CONCLUSION: Both olfactory training methods can improve olfactory function and that the improvement is associated with changes in the structure of olfactory processing areas of the brain.