Ultra-low-dose CBCT: new cornerstone of paranasal sinus imaging.

BACKGROUND: This study evaluates the clinical image quality (IQ) and usability of a sinonasal ultra-low-dose (ULD) cone-beam computed tomography (CBCT) scan. The results are compared to those of a high resolution (HR) CBCT scan to identify the strengths and weaknesses of a ULD CBCT protocol. METHODOLOGY: Sixty-six anatomical sites in 33 subjects were imaged twice using two imaging modalities: HR CBCT (Scanora 3Dx scanner; Soredex, Tuusula, Finland) and ULD CBCT (Promax 3D Mid scanner; Plandent, Helsinki, Finland). IQ, opacification and obstruction, structural features and operative usability were assessed. RESULTS: The overall IQ in subjects with 'no or minor opacification' was excellent: 100% (HR CBCT) and 99% (ULD CBCT) of ratings were evaluated as sufficient for every structure. Increased opacification reduced the quality of both imaging modalities, resulting conchtoethmoidectomy, frontal sinusotomy, sphenotomy and posterior ethmoidectomy in cases with greater opacification. CONCLUSIONS: IQ of paranasal ULD CBCT is sufficient for clinical diagnostics and should be considered for surgical planning. We recommend it as the primary imaging protocol for all patients who meet imaging criteria due to recurrent or chronic nasal symptoms. Additional or conventional imaging might be needed for patients with extensive chronic rhinosinusitis and/or indications of frontal sinus involvement.

Diagnostic Accuracy of Symptoms, Endoscopy, and Imaging Signs of Chronic Rhinosinusitis Without Nasal Polyps Compared to Allergic Rhinitis.

Objectives The diagnosis of chronic rhinosinusitis without nasal polyps (CRSsNP) and distinguishing it from allergic rhinitis is difficult. Yet, early detection of CRSsNP is important to prevent progressive and severe chronic rhinosinusitis. Our aim was to compare diagnostic accuracy of symptoms, endoscopy, and imaging signs of CRSsNP and allergic rhinitis -only phenotypes. Setting Prospective controlled follow-up study. Participants Forty-two nonsmoking patients visiting tertiary care due to CRSsNP and 19 nonsmoking volunteer controls with allergic rhinitis filled a symptoms questionnaire and underwent nasal endoscopy off-seasonally. All CRSsNP patients underwent computed tomography scans of paranasal sinuses. All the allergic rhinitis control subjects and 14 of the CRSsNP patients underwent sinus magnetic resonance imaging. Results Radiologic Lund-Mackay score, duration of symptoms, visual analogue scale scores of symptoms, and Sinonasal Outcome Test 22 were significantly higher in the CRSsNP group compared to allergic rhinitis control group. These factors also correlated in part with each other. Endoscopic score did not correlate with other factors, nor did it differ between CRSsNP and allergic rhinitis groups. The highest area under curve value was demonstrated for visual analogue scale score of facial pain/pressure (0.93) and score ≥4/10 showed 60% sensitivity and 95% specificity for detecting CRSsNP group ( P < .001). Radiologic sign of obstructed osteomeatal complex showed 100% specificity and 38% sensitivity for detecting CRSsNP group ( P < .001). Conclusions CRSsNP phenotype could be primarily distinguished from allergic rhinitis by higher facial pain/pressure score and secondarily by radiologic sings of obstructed ostiomeatal complex and higher Lund-Mackay score. Endoscopic score has limited value in distinguishing CRSsNP from allergic rhinitis.

A prospective, randomized clinical study comparing drug eluting stent therapy and intranasal corticoid steroid therapy in the treatment of patients with chronic rhinosinusitis.

OBJECTIVES: To conduct the first prospective, randomized controlled clinical trial comparing the efficacy of a drug-eluting stent (DES) (the Relieva StratusTM MicroFlow Spacer) and topical intranasal corticosteroid therapy in patients with chronic rhinosinusitis (CRS). METHODS: Sixty-three adult patients with ethmoiditis were randomized into either the DES group (n=34) or nasal spray group (n=29). The main outcome variable was the Sinonasal Outcome Test 22, Visual Analogue Scale, nasal endoscopy, rhinometric measurements were performed at the beginning of the study, after three months and six months of follow-up. RESULTS: Both treatments significantly improved quality of the life with no significant difference being found between the two groups. The VAS score decreased in both groups: improvements were significant at three and six months in the nasal spray group, but in the DES group a significant difference was noted only at three months. There was a statistically significant increase in total nasal cavity volumes in the corticosteroid spray group, but not in the DES group. CONCLUSION: We found that patients benefitted from DES and the corticosteroid nasal spray. We could not find any significant difference between the treatments, except the greater increase in the total nasal cavity volumes favouring the nasal spray group. Because of the very good results for the nasal spray and the much higher material and operating room costs associated with DES, we cannot recommend the use of DES over nasal spray as a monotherapeutic treatment for CRS.

Low lymphatic vessel density associates with chronic rhinosinusitis with nasal polyps.

OBJECTIVES: Chronic rhinosinusitis with and without nasal polyps (CRSwNP and CRSsNP) and antrochoanal polyps (ACP) are different upper airway inflammation phenotypes with different pathomechanisms. In order to understand the development of tissue edema, the present study aimed to evaluate lymphatic vessel density in CRSsNP, CRSwNP and ACP. MATERIALS AND METHODS: 120 retrospective nasal and maxillary sinus specimens were stained immunohistochemically with a von Willebrand factor polyclonal antibody recognizing vascular and lymphatic endothelium, and with a podoplanin monoclonal antibody recognizing lymphatic endothelium. Vessels were studied by microscopy in a blinded fashion, and the vessel density and the relative density of lymphatic vessels were calculated. Patient characteristic factors and follow-up data of in average 9 years were collected from patient records. RESULTS AND CONCLUSION: In the nasal cavity, the low absolute and relative density of vessels and of lymphatic vessels was associated with CRSwNP and ACP tissues compared to control inferior turbinate. This was observed also in the inflammatory hotspot area. In the maxillary sinus, lower absolute and relative density of lymphatic vessels associated with the CRSwNP phenotype. High lymphatic vessel density in polyp tissue associated with the need for revision CRS-surgery. As a conclusion, low density of lymphatic vessels distinguished patients with CRSwNP not only in the hotspot area of polyp tissue, but also in maxillary sinus mucosa. Yet, higher lymphatic vessel density seems to associate with polyp recurrence. Further studies are still needed to explore if formation of nasal polyps could be diminished by intranasal therapeutics affecting lymphangiogenesis.

Genome-wide association study of antisocial personality disorder.

The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53-3.14), P=1.9 × 10(-5)). Two polymorphisms at 6p21.2 LINC00951-LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37-1.85), P=1.6 × 10(-9)) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (ß=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder.

Influence of a HTR2B Stop Codon on Glucagon Homeostasis and Glucose Excursion in Non-Diabetic Men.

Limited data are available about the role of the serotonin 2B (5-HT2B) receptor in the function of human islets. This study aimed to test whether the 5-HT2B receptor contributes to glucose, insulin, and glucagon homeostasis in humans, utilizing a hereditary loss-of-function gene mutation in the receptor, which causes a 50% reduction in the production of the receptor protein in heterozygotes. This clinical study enrolled participants recruited by newspaper advertisements and from mental status examinations. A cohort of participants from a young Finnish founder population composed of 68 non-diabetic males with a mean age of 30 was divided into groups for comparison based on being a 5-HT2B receptor loss-of-function gene mutation (HTR2B Q20*) heterozygote carrier (n=11) or not (n=57). Serum levels of glucose, insulin, and glucagon were measured in a 5 h oral glucose tolerance test using a 75 g glucose challenge. Insulin resistance, insulin sensitivity, and beta cell activity were calculated using the homeostasis model assessment (HOMA2) and whole body insulin sensitivity index (WBISI), as well as the ratio of glucagon to insulin was noted. The areas under the curves (AUCs) were also determined. Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in cerebrospinal fluid (CSF). Covariate adjusted mean score comparisons were applied. Lower glucagon secretion and decreased glucose excursion were observed among HTR2B Q20* carriers as compared with individuals who were homozygotes for the wild-type Q20 allele (controls). No differences in insulin secretion, beta cell activity, insulin resistance, or insulin sensitivity were observed. The glucagon to insulin ratio differed between the HTR2B Q20* carriers and controls. CSF levels of 5-HIAA were similar between groups. Our findings indicate that the 5-HT2B receptor may contribute to the regulation of human glucagon and glucose homeostasis and the interplay between glucagon and insulin secretion.

Pleomorphic adenoma in the nasal cavity: a clinicopathological study of ten cases in Finland.

The objective of the study was to investigate the nationwide occurrence of sinonasal pleomorphic adenoma in Finland. A retrospective study was conducted at The Departments of Otorhinolaryngology-Head and Neck Surgery, and Pathology at the five university hospitals in Finland. Data were obtained by searching for sinonasal pleomorphic adenoma cases in the clinical and histopathological registries at these institutions for the past two to four decades. All patients who had had a histologically proven pleomorphic adenoma in the sinonasal area were included as participants. Ten cases with pleomorphic adenoma of the nasal cavity were found. The majority of these tumours originated in the septum, and there were no malignant transformations. Pleomorphic adenomas of the nasal cavity were found to be extremely rare in this nationwide investigation.

Decrease of nasal airway resistance and alleviations of symptoms after balloon sinuplasty in patients with isolated chronic rhinosinusitis: a prospective, randomised clinical study.

OBJECTIVES: The aim of this study was to evaluate and compare the clinical outcome of balloon sinuplasty and uncinectomy for patients suffering from isolated chronic rhinosinusitis of the maxillary sinus. DESIGN: A prospective, randomised, non-blinded, controlled trial was conducted. SETTING: The study was carried out at the Department of Otolaryngology, Tampere University Hospital, Finland. PARTICIPANTS: Adult patients with symptomatic isolated chronic or recurrent rhinosinusitis without severe findings in the sinuses, as documented in the sinus' Computer Tomography scan and clinical examination, were randomised into two groups: uncinectomy and balloon sinuplasty. MAIN OUTCOME MEASURES: The variables in our study are the Sinonasal Outcome Test-22 (SNOT 22), acoustic rhinometry and rhinomanometry. These parameters were analysed preoperatively and postoperatively (after 3 and 6 months). RESULTS: The preliminary results of our study have been previously published. Both balloon sinuplasty and uncinectomy significantly improved almost all the parameters of SNOT22 (P < 0.05), with no significant difference being found between these two groups (P > 0.05). Based on rhinomanometry results, airway resistance decreased after treatment. Regarding adverse effects, balloon sinuplasty was significantly associated with a lesser risk of synechia. CONCLUSIONS: Both balloon sinuplasty and uncinectomy improved the quality of life and decreased upper airway resistance of patients with mild, isolated chronic or recurrent rhinosinusitis. The smaller risk of postoperative synechiae with balloon sinuplasty combined with its promising efficiency could partially compensate for its high material cost.

The endoscopic study of human middle ear mucociliary transport.

The mucociliary clearance (MCC) is an important defence mechanism of the middle ear. The mucociliary transport (MCT) is a part of MCC. We measured the duration of MCT and visualised its routes in middle ears of 31 patients (mean age 45 years; range 7-61 years; SD 11.6) with intact tympanic membrane, with ventilated middle ears and without a history of prolonged otitis media. The transition time of indigo carmine dye from the promontory mucosa to the middle ear orifice of the Eustachian tube (ET) was observed with a rigid 30°, 1.7-mm-diameter tympanoscope. The dye took an average of 7 min (range 4.5-15 min; SD 3.4; median 4.5) to reach the ET orifice in 25 (81 %) patients. Three main ciliary pathways were detected: (1) below and parallel to the tensor tympani muscle; (2) downwards, anterior to the round window, and then ascending to the ET; and (3) straight across the promontory.

Impulsive alcohol-related risk-behavior and emotional dysregulation among individuals with a serotonin 2B receptor stop codon.

A relatively common stop codon (Q20*) was identified in the serotonin 2B receptor gene (HTR2B) in a Finnish founder population in 2010 and it was associated with impulsivity. Here we examine the phenotype of HTR2B Q20* carriers in a setting comprising 14 heterozygous HTR2B Q20* carriers and 156 healthy controls without the HTR2B Q20*. The tridimensional personality questionnaire, Brown-Goodwin lifetime aggression scale, the Michigan alcoholism screening test and lifetime drinking history were used to measure personality traits, impulsive and aggressive behavior, both while sober and under the influence of alcohol, and alcohol consumption. Regression analyses showed that among the HTR2B Q20* carriers, temperamental traits resembled a passive-dependent personality profile, and the presence of the HTR2B Q20* predicted impulsive and aggressive behaviors particularly under the influence of alcohol. Results present examples of how one gene may contribute to personality structure and behaviors in a founder population and how personality may translate into behavior.

The effect of adenoidectomy on occlusal development and nasal cavity volume in children with recurrent middle ear infection.

OBJECTIVES: The aim of the study was to examine the effect of adenoidectomy on occlusal/dentoalveolar development and nasal cavity volume in children who underwent tympanostomy tube insertion with or without adenoidectomy due to recurrent episodes of middle ear infection. METHODS: This prospective controlled study consisted of two randomly allocated treatment groups of children, younger than 2 years, who had underwent more than 3-5 events of middle ear infection during the last 6 months or 4-6 events during the last year. At the mean age of 17 months tympanostomy tube placement without adenoidectomy (Group I, n=63) tympanostomy tube placement with adenoidectomy (Group II, n=74) was performed. At the age of 5 years 41 children of the original Group I (14 females, 27 males, mean age 5.2 yrs, SD 0.17) and 59 children of the original Group II (17 females, 42 males, mean age 5.2 yrs, SD 0.18) participated in the re-examination, which included clinical orthodontic examination defining morphological and functional craniofacial status and occlusal bite index to measure upper dental arch dimensions. Acoustic rhinometry and anterior rhinomanometry was made by otorhinolaryngologist at the same day. RESULTS: No statistically significant differences were found between the groups in the frequencies of morphological or functional characteristics or upper dental arch measurements or in the minimal cross-sectional areas or inspiratory nasal airway resistance measurements. CONCLUSION: Combining adenoidectomy with tympanostomy tube insertion in the treatment of recurrent middle ear infection at an early age (under the age of 2 years) does not seem to make any difference in occlusal development in primary dentition at the age of 5 years as compared to tympanostomy tube insertion only. Since adenoid size was not evaluated, the findings do not allow interpretation that hypertrophic adenoids should not be removed in children with continuous mouth breathing or sleep disordered breathing.

Genetic background of extreme violent behavior.

In developed countries, the majority of all violent crime is committed by a small group of antisocial recidivistic offenders, but no genes have been shown to contribute to recidivistic violent offending or severe violent behavior, such as homicide. Our results, from two independent cohorts of Finnish prisoners, revealed that a monoamine oxidase A (MAOA) low-activity genotype (contributing to low dopamine turnover rate) as well as the CDH13 gene (coding for neuronal membrane adhesion protein) are associated with extremely violent behavior (at least 10 committed homicides, attempted homicides or batteries). No substantial signal was observed for either MAOA or CDH13 among non-violent offenders, indicating that findings were specific for violent offending, and not largely attributable to substance abuse or antisocial personality disorder. These results indicate both low monoamine metabolism and neuronal membrane dysfunction as plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5-10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.

AIP inactivation leads to pituitary tumorigenesis through defective Gαi-cAMP signaling.

The aryl hydrocarbon receptor interacting protein (AIP) is a tumor-suppressor gene underlying the pituitary adenoma predisposition. Thus far, the exact molecular mechanisms by which inactivated AIP exerts its tumor-promoting action have been unclear. To better understand the role of AIP in pituitary tumorigenesis, we performed gene expression microarray analysis to examine changes between Aip wild-type and knockout mouse embryonic fibroblast (MEF) cell lines. Transcriptional analyses implied that Aip deficiency causes a dysfunction in cyclic adenosine monophosphate (cAMP) signaling, as well as impairments in signaling cascades associated with developmental and immune-inflammatory responses. In vitro experiments showed that AIP deficiency increases intracellular cAMP concentrations in both MEF and murine pituitary adenoma cell lines. Based on knockdown of various G protein α subunits, we concluded that AIP deficiency leads to elevated cAMP concentrations through defective Gαi-2 and Gαi-3 proteins that normally inhibit cAMP synthesis. Furthermore, immunostaining of Gαi-2 revealed that AIP deficiency is associated with a clear reduction in Gαi-2 protein expression levels in human and mouse growth hormone (GH)-secreting pituitary adenomas, thus indicating defective Gαi signaling in these tumors. By contrast, all prolactin-secreting tumors showed prominent Gαi-2 protein levels, irrespective of Aip mutation status. We additionally observed reduced expression of phosphorylated extracellular signal-regulated kinases 1/2 and cAMP response element-binding protein levels in mouse and human AIP-deficient somatotropinomas. This study implies for the first time that a failure to inhibit cAMP synthesis through dysfunctional Gαi signaling underlies the development of GH-secreting pituitary adenomas in AIP mutation carriers.

Quality of life after endoscopic sinus surgery or balloon sinuplasty: a randomized clinical study.

OBJECTIVES: To conduct the first prospective randomized controlled trial that evaluates and compares the clinical outcome and impact of ballonsinuplasty and endoscopic sinus surgery (ESS) on the quality of life of patients suffering from chronic or recurrent rhinosinusitis (CRS) of the maxillary sinus. METHODS: Adult patients with symptomatic chronic or recurrent rhinosinusitis without severe findings in the sinuses, as documented in the sinus' Computer Tomography scan and clinical exam, were randomized in 2 groups: ESS and Balloon Sinuplasty.The main variable in our study is the Sinonasal Outcome Test-22 (SNOT 22) and its parameters. These parameters were analysed preoperatively and at 3 months, postoperatively. RESULTS: There was a subjective improvement in symptoms after surgery. We also noticed an objective improvement in the quality of life of our patients seen as a decrease in the total SNOT 22 score. Both balloon sinuplasty and ESS significantly improved almost all the parameters of SNOT22, with no significant difference being found between these two groups. CONCLUSION: Both balloon sinuplasty and endoscopic sinus surgery improved the quality of life of patients with mild chronic or recurrent rhinosinusitis. However, the remarkably higher material cost of balloon sinuplasty compared to ESS sets limits on its broad use. There is an obvious need for further study to find out if, as an office procedure, balloon sinuplasty could deliver cost-savings high enough to cover the higher material cost of balloon sinuplasty. Our study was, however, too small to enable firm conclusions to be drawn.

Computed tomography findings after endoscopic sinus surgery with preserving or enlarging maxillary sinus ostium surgery.

Endoscopic sinus surgery (ESS) is the main surgical approach in the treatment of chronic rhinosinusitis (CRS) after failure of medical treatment. ESS is based on the theory that obstruction of the maxillary sinus ostium is mainly behind the pathogenesis of CRS. Controversy remains concerning the enlargement of the natural maxillary sinus ostium. The aim of this study was to compare computed tomography (CT) findings after preservation or enlargement of the maxillary sinus ostium. Thirty patients with non-polypous CRS underwent randomized endoscopic sinus surgery with uncinectomy on one side and additional middle meatal antrostomy on the other side. Lund-Mackay (LM) scores and the ostium diameters were analysed from CT scans taken preoperatively and nine months postoperatively, and were used for comparison of the two operative techniques. In addition, the correlation between CT findings and subjective outcomes was studied. Comparison of the preoperative and postoperative CT scans revealed that significant reduction of LM score was achieved on both sides, regardless of the type of procedure performed. The postoperative area of the ostium remained significantly larger on the antrostomy side compared to the uncinectomy side. A large maxillary sinus ostium size seems to associate with lower postoperative LM score, but does not seem to provide superior symptom relief.

Indoleamine 2,3-dioxygenase expression is associated with chronic rhinosinusitis with nasal polyps and antrochoanal polyps.

Chronic rhinosinusitis without and with nasal polyps (CRSwNP and CRSsNP), and antrochoanal polyps are different phenotypes with different pathomechanisms. Indoleamine 2,3-dioxygenase (IDO) is an enzyme expressed in many cells involved in the catabolism of the essential amino acid tryptophan to kynurenine. IDO might have a role in allergic airway inflammation. The aim was to evaluate if IDO expression is associated with CRSsNP, CRSwNP, or ACP. One hundred fifty specimens from the nasal cavity and sinus mucosa were immunohistochemically stained with mAb anti-IDO. The expression of epithelial and leukocyte IDO was associated with CRSwNP and ACP. The presence of ASA intolerance, asthma, atopy, smoking and use of medication did not significantly change the results. The different expression of IDO could putatively indicate the differences in the pathomechanisms of CRSsNP, CRSwNP and ACP. Further studies on the role of IDO in upper airways pathologies are required.

Pharmacokinetics of azithromycin in serum and sinus fluid after administration of extended-release and immediate-release formulations in patients with acute bacterial sinusitis.

As high drug levels at the infection site are desirable for optimal activity, this study explored whether one dose of azithromycin extended release (AZ-ER) achieved higher azithromycin exposure in sinus fluid than azithromycin immediate release (AZ-IR) in adults with acute bacterial sinusitis. Subjects received AZ-ER (2g single dose; n=5) or AZ-IR (500mg daily for 3 days; n=4) and blood and sinus aspirates were collected until 120 h after initial dosing. Within 24 h, exposure was four- and three-fold higher with AZ-ER than with AZ-IR in serum and sinus fluid, respectively. Sinus fluid exposure was five- and three-fold higher than serum for AZ-IR and AZ-ER, respectively. Azithromycin concentrations in sinus fluid were maintained up to 120 h.

Effect of endoscopic sinus surgery on antral mucociliary clearance.

Endoscopic sinus surgery (ESS) is the most used surgical approach in the treatment of chronic and recurrent maxillary rhinosinusitis. However, it still remains unclear how well surgery restores the mucociliary function in damaged maxillary sinus mucosa. There is also controversy whether to enlargen the natural ostium or not. We examined the mucociliary clearance (MCC) of maxillary sinuses in 27 patients with chronic and recurrent rhinosinusitis. On one side only an uncinectomy was done, on the contralateral side a middle meatal antrostomy was additionally performed. The mucociliary clearance (MCC) was measured in both sides preoperatively and 9 months after the operation. Measurements of the mucociliary clearance in maxillary sinuses were done using an isotope method. Preoperative mean residual activity on the uncinectomy side was 87.2 % and postoperative mean residual activity 94.1 %. On the middle meatal antrostomy side mean preoperative residual activity was 92.3 % and postoperative mean residual activity 88.4 %. Residual activity was considered as good (< or = 50 %) on the uncinectomy side in 2 sinuses (7.4 %) preoperatively and in 1 sinus (3.7 %) postoperatively. On the middle meatal antrostomy side residual activity was considered good in 1 sinus (3.7 %) preoperatively and in 4 sinuses (14.8 %) postoperatively. Mucociliary function remained poor even 9 months postoperatively. Surgery did not significantly improve the mucociliary function of maxillary sinus mucosa in chronic or recurrent rhinosinusitis. There was no statistical difference between operative techniques. In this study it seemed however, that uncinectomy combined with the enlargening of the natural ostium may restore maxillary sinus mucociliary clearance (MCC) better than uncinectomy alone.

Investigations of dipole localization accuracy in MEG using the bootstrap.

We describe the use of the nonparametric bootstrap to investigate the accuracy of current dipole localization from magnetoencephalography (MEG) studies of event-related neural activity. The bootstrap is well suited to the analysis of event-related MEG data since the experiments are repeated tens or even hundreds of times and averaged to achieve acceptable signal-to-noise ratios (SNRs). The set of repetitions or epochs can be viewed as a set of independent realizations of the brain's response to the experiment. Bootstrap resamples can be generated by sampling with replacement from these epochs and averaging. In this study, we applied the bootstrap resampling technique to MEG data from somatotopic experimental and simulated data. Four fingers of the right and left hand of a healthy subject were electrically stimulated, and about 400 trials per stimulation were recorded and averaged in order to measure the somatotopic mapping of the fingers in the S1 area of the brain. Based on single-trial recordings for each finger we performed 5000 bootstrap resamples. We reconstructed dipoles from these resampled averages using the Recursively Applied and Projected (RAP)-MUSIC source localization algorithm. We also performed a simulation for two dipolar sources with overlapping time courses embedded in realistic background brain activity generated using the prestimulus segments of the somatotopic data. To find correspondences between multiple sources in each bootstrap, sample dipoles with similar time series and forward fields were assumed to represent the same source. These dipoles were then clustered by a Gaussian Mixture Model (GMM) clustering algorithm using their combined normalized time series and topographies as feature vectors. The mean and standard deviation of the dipole position and the dipole time series in each cluster were computed to provide estimates of the accuracy of the reconstructed source locations and time series.