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STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a very prevalent disease and its diagnosis is based on polysomnography (PSG). We investigated whether snoring-sound-, very low frequency electrocardiogram (ECG-VLF)- and thoraco-abdominal effort- PSG signal entropy values could be used as surrogate markers for detection of OSA and OSA severity classification. METHODS: The raw data of the snoring-, ECG- and abdominal and thoracic excursion signal recordings of two consecutive full-night PSGs of 86 consecutive patients (22 female, 53.74 ± 12.4 years) were analyzed retrospectively. Four epochs (30 s each, manually scored according to the American Academy of Sleep Medicine standard) of each sleep stage (N1, N2, N3, REM, awake) were used as the ground truth. Sampling entropy (SampEn) of all the above signals was calculated and group comparisons between the OSA severity groups were performed. In total, (86x4x5 = )1720 epochs/group/night were included in the training set as an input for a support vector machine (SVM) algorithm to classify the OSA severity classes. Analyses were performed for first- and second-night PSG recordings separately. RESULTS: Twenty-seven patients had mild (RDI = ≥ 5/h but <15/h), 21 patients moderate (RDI ≥15/h but <30/h) and 23 patients severe OSA (RDI ≥30/h). Fifteen patients had an RDI <5/h and were therefore considered non-OSA. Using SE on the above three PSG signal data and using a SVM pipeline, it was possible to distinguish between the four OSA severity classes. The best metric was snoring signal-SE. The area-under-the-curve (AUC) calculations showed reproducible significant results for both nights of PSG. The second night data were even more significant, with non-OSA (R) vs. light OSA (L) 0.61, R vs. moderate (M) 0.68, R vs. heavy OSA (H) 0.84, L vs. M 0.63, M vs. H 0.65 and L vs. H 0.82. The results were not confounded by age or gender. CONCLUSIONS: SampEn of either snoring-, very low ECG-frequencies- or thoraco-abdominal effort signals alone may be used as a surrogate marker to diagnose OSA and even predict OSA severity. More specifically, in this exploratory study snoring signal SampEn showed the greatest predictive accuracy for OSA among the three signals. Second night data showed even more accurate results for all three parameters than first-night recordings. Therefore, technologies using only parts of the PSG signal, e.g. sound-recording devices, may be used for OSA screening and OSA severity group classification.

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Recently, interest has been growing to understand the underlying dynamic directional relationship between simultaneously activated regions of the brain during motor task performance. Such directionality analysis (or effective connectivity analysis), based on non-invasive electrophysiological (electroencephalography-EEG) and hemodynamic (functional near infrared spectroscopy-fNIRS; and functional magnetic resonance imaging-fMRI) neuroimaging modalities can provide an estimate of the motor task-related information flow from one brain region to another. Since EEG, fNIRS and fMRI modalities achieve different spatial and temporal resolutions of motor-task related activation in the brain, the aim of this study was to determine the effective connectivity of cortico-cortical sensorimotor networks during finger movement tasks measured by each neuroimaging modality. Nine healthy subjects performed right hand finger movement tasks of different complexity (simple finger tapping-FT, simple finger sequence-SFS, and complex finger sequence-CFS). We focused our observations on three cortical regions of interest (ROIs), namely the contralateral sensorimotor cortex (SMC), the contralateral premotor cortex (PMC) and the contralateral dorsolateral prefrontal cortex (DLPFC). We estimated the effective connectivity between these ROIs using conditional Granger causality (GC) analysis determined from the time series signals measured by fMRI (blood oxygenation level-dependent-BOLD), fNIRS (oxygenated-O2Hb and deoxygenated-HHb hemoglobin), and EEG (scalp and source level analysis) neuroimaging modalities. The effective connectivity analysis showed significant bi-directional information flow between the SMC, PMC, and DLPFC as determined by the EEG (scalp and source), fMRI (BOLD) and fNIRS (O2Hb and HHb) modalities for all three motor tasks. However the source level EEG GC values were significantly greater than the other modalities. In addition, only the source level EEG showed a significantly greater forward than backward information flow between the ROIs. This simultaneous fMRI, fNIRS and EEG study has shown through independent GC analysis of the respective time series that a bi-directional effective connectivity occurs within a cortico-cortical sensorimotor network (SMC, PMC and DLPFC) during finger movement tasks.

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Voxel based morphometry (VBM) is an automated analysis technique which allows voxel-wise comparison of mainly grey-matter volumes between two magnetic resonance images (MRI). Two main analysis processes in VBM are possible. One is cross-sectional data analysis, where one group is compared with another to depict see the regions in the brain, which show changes in their grey-matter volume. Second is longitudinal data analysis, where MRIs, taken at different time points, are compared to see the regions in the brain that show changes in their grey matter volume for one time point with respect to another time point. Both types of analyses require pre-processing steps before performing the statistical analysis. In this study, we examined grey matter differences for patients with blepharospasmus (BFS) before and after treatment, at two different time points. The main evidence base therapy for this condition is the "botulinum toxin" injection in the respective muscles. The main aim of this study was to look at the effects of different pre-processing steps, namely, normalization and smoothing on the results of the longitudinal data analysis. A second aim was to analyze structural grey-matter differences before and after the treatment. Our results showed that the DARTEL normalization and the lower width for smoothing as preprocessing steps delivered pathophysiological plausible results. The longitudinal analysis revealed significant temporal differences after the injection of the botulinum toxin injection mainly in patients with BFS.

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The most well-known non-invasive electric and magnetic field measurement modalities are the electroencephalography (EEG) and magnetoencephalography (MEG). The first aim of the study was to implement the recently developed realistic head model which uses an integrative approach for both the modalities. The second aim of this study was to find the network of coherent sources and the modes of interactions within this network during isometric contraction (ISC) at (15-30 Hz) in healthy subjects. The third aim was to test the effective connectivity revealed by both the modalities analyzing them separately and combined. The Welch periodogram method was used to estimate the coherence spectrum between the EEG and the electromyography (EMG) signals followed by the realistic head modelling and source analysis method dynamic imaging of coherent sources (DICS) to find the network of coherent sources at the individual peak frequency within the beta band in healthy subjects. The last step was to identify the effective connectivity between the identified sources using the renormalized partial directed coherence method. The cortical and sub-cortical network comprised of the primary sensory motor cortex (PSMC), secondary motor area (SMA), and the cerebellum (C). The cortical and sub-cortical network responsible for the isometric contraction was similar in both the modalities when analysing them separately and combined. The SNR was not significantly different between the two modalities separately and combined. However, the coherence values were significantly higher in the combined modality in comparison to each of the modality separately. The effective connectivity analysis revealed plausible additional connections in the combined modality analysis.

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Parkinsonian tremor (PD), essential tremor (ET) and voluntarily mimicked tremor represent fundamentally different motor phenomena, yet, magnetoencephalographic and imaging data suggest their origin in the same motor centers of the brain. Using EEG-EMG coherence and coherent source analysis we found a different pattern of corticomuscular delays, time courses and central representations for the basic and double tremor frequencies typical for PD suggesting a wider range defective oscillatory activity. For the basic tremor frequency similar central representations in primary sensorimotor, prefrontal/premotor and diencephalic (e.g. thalamic) areas were reproduced for all three tremors. But renormalized partial directed coherence of the spatially filtered (source) signals revealed a mainly unidirectional flow of information from the diencephalon to cortex in voluntary tremor, e.g. a thalamocortical relay, as opposed to a bidirectional subcortico-cortical flow in PD and ET promoting uncontrollable, e.g. thalamocortical, loop oscillations. Our results help to understand why pathological tremors although originating from the physiological motor network are not under voluntary control and they may contribute to the solution of the puzzle why high frequency thalamic stimulation has a selective effect on pathological tremor leaving voluntary movement performance almost unaltered.

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Directionality analysis of signals originating from different parts of brain during motor tasks has gained a lot of interest. Since brain activity can be recorded over time, methods of time series analysis can be applied to medical time series as well. Granger Causality is a method to find a causal relationship between time series. Such causality can be referred to as a directional connection and is not necessarily bidirectional. The aim of this study is to differentiate between different motor tasks on the basis of activation maps and also to understand the nature of connections present between different parts of the brain. In this paper, three different motor tasks (finger tapping, simple finger sequencing, and complex finger sequencing) are analyzed. Time series for each task were extracted from functional magnetic resonance imaging (fMRI) data, which have a very good spatial resolution and can look into the sub-cortical regions of the brain. Activation maps based on fMRI images show that, in case of complex finger sequencing, most parts of the brain are active, unlike finger tapping during which only limited regions show activity. Directionality analysis on time series extracted from contralateral motor cortex (CMC), supplementary motor area (SMA), and cerebellum (CER) show bidirectional connections between these parts of the brain. In case of simple finger sequencing and complex finger sequencing, the strongest connections originate from SMA and CMC, while connections originating from CER in either direction are the weakest ones in magnitude during all paradigms.

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Human peripheral blood eosinophils adhered specifically to microtitre plates coated with plasma fibronectin (Fn) in a dose- and time-dependent fashion. Adhesion was optimal at 60 min at a concentration of 100 micrograms/ml. Adherence to Fn was up-regulated by platelet-activating factor (PAF; optimum concentration of 10(-6) M) and was significantly inhibited by a polyclonal anti-Fn antibody (P < 0.05). The following evidence suggested that eosinophil adhesion to Fn was mediated by alpha 4 beta 1: (1) eosinophil adherence to Fn was not inhibited by an Arg-Gly-Asp-Ser (RGDS) synthetic peptide; (2) there was a dose-dependent adherence of eosinophils to microtitre plates coated with the 40,000 MW proteolytic fragment of Fn that contains the CS-1 alpha 4 beta 1 binding region, whereas adherence to the 120,000 MW chymotryptic fragment of Fn, which contains the RGD-dependent binding site, was weak and only observed at high concentrations (> 250 micrograms/ml); (3) significant inhibition of eosinophil adherence to Fn was achieved by monoclonal antibodies (mAb) against the alpha chain of VLA-4 but not by a mAb against CD45 or a mouse myeloma antibody as negative controls. After adhesion to Fn, eosinophils were investigated for their capacity to release leukotriene C4 in response to stimulation with a suboptimal concentration of calcium ionophore (2 x 10(-6) M). Significant enhancement of release was detected with Fn-coated plates but not with the control bovine serum albumin (BSA) (P < 0.01). Furthermore, this enhancement was significantly inhibited by the alpha 4 beta 1 mAb HP2/1 (P < 0.05) but not by an anti-CD45 mAb. From these studies we conclude that (1) alpha 4 beta 1 (VLA-4) integrin is a major receptor for Fn on human eosinophils and (2) adhesion to Fn may prime eosinophils for mediator release during allergic inflammation.

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We have investigated the effect of adhesion to fibronectin (Fn) on the survival of eosinophils in culture. Peripheral blood eosinophils from normal human donors were separated by immunomagnetic selection and cultured in RPMI on Fn- (100 micrograms/ml) coated microtiter plates for up to 96 h. Survival was measured by trypan blue exclusion. There was a significant enhancement of eosinophil survival with Fn as compared with both bovine serum albumin-coated and uncoated wells (p < 0.05-0.01). Fn-induced eosinophil survival was comparable to that obtained with exogenous interleukin 3 (IL-3) or granulocyte/macrophage colony-stimulating factor (GM-CSF) and was inhibitable by antibodies against Fn, very late antigen 4 (VLA-4), IL-3, and GM-CSF. Supernatants from Fn-, but not BSA-coated wells contained picogram amounts of IL-3 and GM-CSF, and eosinophils cultured on Fn for 24 h expressed mRNA for GM-CSF as determined by in situ hybridization. Therefore, Fn prolongs eosinophil survival in culture by triggering autocrine generation of cytokines by eosinophils. Since neutrophils lack VLA-4, this could provide a partial explanation for the preferential accumulation of eosinophils at sites of allergic inflammation, as well as the predominant tissue localization of eosinophils in healthy individuals.

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The pharmacological specificity of histamine-induced enhancement of human eosinophil C3b rosettes was studied using H1- and H2-receptor agonists and antagonists. The H1 agonist, 2-(2-aminoethyl) thiazole (2-2-AET), enhanced eosinophil C3b rosettes in a comparable fashion to that of histamine, whereas the H2 agonists, 4-methylhistamine and Dimaprit, were without effect. Similarly, rosette enhancement by histamine was inhibited by the H1 antagonists, chlorpheniramine and mepyramine, but not by the H2 antagonists, burimamide and metiamide. These experiments indicate that enhancement of eosinophil C3b rosettes by histamine, a mechanism which might be of importance in the amplification of complement-dependent killing of helminthic larvae, is predominantly H1-receptor-dependent.

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