脑内电流偶极子动态参数的反演研究

多通道高时间分辨率脑磁探测系统为反演脑内动态电活动参数提供了一种可能性。通过分析头表面某一边疆时间片段上时域－空域磙场数据矩阵的奇异值序列分布特征,可以确定相应信号矩阵的秩,从而获得某一时段脑内电活动源的数目,进而在该时段内选用相应的源数目,并利用优化算法,即可反演出脑内电活动源的动态参数。模拟计算及对声音刺激的诱发脑磁源的计算均表明这一方法是有效的。     

Confidence limits for the parameter estimation in the dipole localization method on the basis of spatial correlation of background EEG

Summary A new residual function in the inverse problem of equivalent dipole localization methods is proposed which is based on the spatial correlation of the background EEG. This residual has the advantage that it allows the calculation of confidence limits for dipole model parameters. The method was applied to VEP data, and it was studied how the localization precision depends on the recording time of the EEG. It was found that the tangential position of an equivalent dipole can be located at 99% confidence in a region of the order 7 × 7mm for a head radius of 10cm, while the 99% confidence interval of the depth estimate is approximately 1cm, with a recording time of 20 minutes. It was also observed that an EEG recording time of more than 10–15 minutes is needed to obtain stable localization precision estimates.     

Sequence-sensitive subcomponents of P300: Topographical analyses and dipole source localization

P300 amplitude and reaction time (RT) are strongly affected by the sequence of events preceding the eliciting stimulus. Sommer, Leuthold and Soetens (1999) found that robust sequential effects in P300 amplitude could be dissociated from more variable sequential effects in RTs. However, global changes in P300 amplitude and topography gave rise to the suggestion that sequential effects are specific for a subcomponent of P300 that is separate from and anterior to the classical parietal P300. Here, confirming evidence for dissociable subcomponents of P300 is reported from two experiments. Independent component analysis separated a centrally distributed sequence-sensitive subcomponent from a more parietal subcomponent. Subsequent dipole source analysis indicated a deep mesial source for the sequence-sensitive subcomponent. Overlap with reafferent somatosensory activity appears to be responsible for an apparent lateralization of this component towards the hemisphere ipsilateral to the responding hand.     

Voltage-Based Versus Factor Score-Based Source Localization Analyses of Electrophysiological Brain Activity: A Comparison

Summary Though, traditionally, electrophysiological recordings have been limited to provide temporal information on neural activity, the development of mathematical algorithms capable of solving the inverse problem is facilitating, in recent years, the access to spatial information (i.e., on the origin of neural activation). This study explored a new strategy in order to increase the reliability of inverse problem solutions: applying these algorithms on factor scores (and not on voltages), a parameter that can be defined as clean amplitude. Factor scores derive from Principal Component Analysis (PCA) applied to event-related potentials (ERPs). The main advantage of PCA is its capability to extract and quantify ERP components free of the influence of adjacent or subjacent components. The LORETA algorithm for source localization was applied on peak voltage, average voltage and factor scores for the motor potential recorded from 25 subjects, who had to repeatedly press a button with their right hand. The solutions given by LORETA in these three modalities were compared. The motor potential, a negative wave that begins just before any voluntary movement and is centrally distributed in the scalp, is particularly useful to the scope of this study, since its origin is known: contralateral motor cortex. Results show that the three modalities (peak voltage, mean voltage and factor scores) provided the same main focus (left motor cortex), though the cleanest solution (i.e., the main focus was more salient with respect to other secondary, noisy foci) was achieved by the factor scorebased LORETA.     

The usefulness of the Laplacian in principal component analysis and dipole source localization

Summary Evoked potentials are difficult to analyze because multiple sources are active simultaneously. Principal component analysis and dipole localization are two techniques that have been used to disentangle overlapping sources. Both of these techniques have problems. Principal component analysis suffers from a rotation ambiguity. Dipole localization suffers from biases when the model used to derive the sources from the scalp potentials is misspecified. Using computer simulations we demonstrate that by applying both of these techniques to the Laplacian of the voltages rather than to the raw voltages the problems associated with the two techniques are reduced. Computer programs for the analyses are presented in an Appendix.Supported by grant EY04776 from the National Institutes of Health. We would like to thank Amnon Silverstein for his help with icosohedra.     

Generators of visual evoked potentials for faces and eyes in the human brain as determined by dipole localization

Human visual evoked potentials were recorded during presentation of photos of human and animal faces and various face features. Negative waves with approximate peak latencies of 165 msec (N170) were bilaterally recorded from the occipito-temporal regions. Mean peak latencies of the N170 were shorter for faces than eyes only. Analyses of amplitudes of evoked potentials indicated that the N170 elicited by faces reflected activity of a specific neural system which was insensitive to detailed differences among individual faces regardless of species, and consequently suggest that this system might function to detect existence of faces in general. On the other hand, the mean amplitude of the N170 elicited by human eyes was significantly larger than those by animal eyes. These differences in response latencies and amplitudes of the N170 suggest existence of at least 2 different visual evoked potentials with similar latencies (i.e., N170) which are sensitive to faces in general and human eyes, respectively. Dipole source localization analysis indicated that dipoles for the N170 elicited by eyes were located in the posterior inferior temporal gyrus, and those for faces, located initially in the same region, but moved toward the fusiform and lingual gyri at the late phase of the N170. The results indicated that information processing of faces and eyes separated at least as early as the latency of the N170 at the posterior inferior temporal gyrus as well as the fusiform and lingual gyri, and might provide neurophysiological and anatomical bases to an initial structural encoding stage of human faces.     

Precision of dipole localization in a spherical volume conductor: A comparison of referential EEG,magnetoencephalography and scalp current density methods

Summary In this study, we determined the influence of dipole orientation, dipole location, and number of recording sites on the precision of dipole localization in a spherical volume conductor. We compared localization from referential EEG (R-EEG), scalp current density EEG (SCD-EEG) and magnetoencephalography (MEG). Dipole orientation had a small influence on the precision of dipole localization for R-EEG and SCD-EEG. Dipole location relative to the recording sites, dipole depth, and number of recording channels strongly influenced the precision of dipole localization. Assuming equal signal to noise conditions for each recording method, MEG and SCD-EEG had a similar precision for dipole localization of a single tangential dipole source and both methods were more precise than R-EEG. However, SCD-EEG was inferior to MEG for distinguishing a single tangential current source from a pair of deeper radial current sources. In summary, these results suggest that the MEG will be most useful for localization of multiple simultaneous dipole sources.     

MRI prior computation and parallel tempering algorithm: a probabilistic resolution of the MEG/EEG inverse problem

Since the MEG inverse problem is ill-posed and admits many possible solutions, it is not possible to give it a single " true" answer. Therefore, we propose here to use a specific probabilistic algorithm to map the full probability distribution of the MEG sources with Markov Chain Monte Carlo methods. Using a Bayesian approach, the probability of the MEG solutions is expressed as the product of the likelihood by the prior probability. To compute the prior and constrain the MEG inverse problem resolution, MRI data are also acquired and automatically processed to determine the brain position and volume. We then use Parallel Tempering algorithm to estimate the full posterior probability and determine the likely solutions of the inverse problem. We illustrate the method with results obtained from the analysis of somatosensory data. This illustrates both the MRI processing for the prior computation, and how the knowledge of the full posterior probability distribution can be used to estimate the position of the sources, as well as their likely extension.     

Septal localization by membrane targeting sequences and a conserved sequence essential for activity at the COOH-terminus of Bacillus subtilis cardiolipin synthase

The acidic phospholipid cardiolipin (CL) is localized on polar and septal membranes and plays an important physiological role in Bacillus subtilis cells. ClsA, the enzyme responsible for CL synthesis, is also localized on septal membranes. We found that GFP fusion proteins of the enzyme with NH₂-terminal and internal deletions retained septal localization. However, derivatives with deletions starting from the COOH-terminus (Leu482) ceased to localize to the septum once the deletion passed the Ile residue at 448, indicating that the sequence responsible for septal localization is confined within a short distance from the COOH-terminus. Two sequences, Ile436-Leu450 and Leu466-Leu478, are predicted to individually form an amphipathic α-helix. This configuration is known as a membrane targeting sequence (MTS) and we therefore refer to them as MTS2 and MTS1, respectively. Either one has the ability to affect septal localization, and each of these sequences by itself localizes to the septum. Membrane association of the constructs of this enzyme containing the MTSs was verified by subcellular fractionation of the cells. CL synthesis, in contrast, was abolished after deleting just the last residue, Leu482, in the COOH-terminal four amino acid residue sequence, Ser-Pro-Ile-Leu, which is highly conserved among bacterial CL synthases.     

A novel PCR-based technique using expressed sequence tags and gene homology for murine genetic mapping: localization of the complement genes

The complement system is a cascade of serum proteins and receptors which forms a vital arm of innate immunity and enhances the adaptive immune response. This work establishes the chromosomal localization of four key genes of the murine complement system. Mapping was performed using a novel and rapid PCR restriction length polymorphism method which was developed to exploit the murine expressed sequence tag (EST) database. This technique circumvents the laborious cDNA or genomic cloning steps of other mapping methods by relying on EST data and the prediction of exon-intron boundaries. This method can be easily applied to the genes of other systems, ranging from the interests of the individual researcher to large-scale gene localization projects. Here the complement system, probably one of the most well-characterized areas of immunology, was used as a model system. It was shown that the C3a receptor C1r and C1s genes form an unexpected complement gene cluster towards the telomeric end of chromosome 6. The second mannose binding lectin-associated serine protease gene was mapped to the telomeric end of chromosome 4, which is distinct from other complement-activating serine proteases. These results provide new insights into the evolution of this group of proteins.     

Single oligonucleotide nested PCR: a rapid method for the isolation of genes and their flanking regions from expressed sequence tags

We report on the development of a new PCR technique for the isolation of genomic fragments that flank known DNA sequences. This technique, single oligonucleotide nested (SON)-PCR, relies on only two amplification reactions with two or three nested sequence-specific primers. It allows the isolation of DNA regions located on either side of a known DNA sequence, with high specificity. DNA products of 2 kb in size can be generated that all contain one copy of the same primer at both ends. Sequence analysis of these products indicates that the binding of the primers to non-specific DNA sites mainly depends on their overall complementarity to the target sequence. Moreover, analysis shows that short extensions of the primers can occur during the first amplification reaction and that a 2-bp overlap between subsequent primers can target their annealing to their predecessors sequence. Ninety percent of the DNA products larger than 0.5 kb correspond to fragments of interest and we obtained successful results with various templates and primer sets. SON-PCR therefore seems a very efficient and widely applicable method for the rapid identification of large unknown DNA regions. Based on available expressed sequence tags, this technique was applied to isolate the palH and pacC genes of the phytopathogenic fungus Botrytis cinerea, with their 5 or 3 flanking regions.     

Method for guiding the ablation catheter to the ablation site: a simulation and experimental study

Radiofrequency catheter ablation (RCA) procedures for treating ventricular arrhythmias have evolved significantly over the past several years; however, the use of RCA has been limited due to the difficulty in identifying the appropriate site for ablation. In this study, we investigate the accuracy of a computer algorithm to guide the tip of an ablation catheter to the exit site of the scar tissue or the site of abnormal automaticity (the “target site”). This algorithm involves modeling the body surface potentials corresponding to the wavefront at the target site for ablation and current pulses generated from a pair of electrodes at the tip of the ablation catheter with a single equivalent moving dipole (SEMD) in an infinite homogeneous volume conductor. Despite the fact that the use of the homogeneous volume conductor introduces systematic error in the estimated compared to the true dipole location, we find that the systematic error had minor influence in the ability of the algorithm to accurately guide the tip of the ablation catheter to the ablation site and the overall error (1.9 ± 1.1 mm) in the left ventricle is adequate for RCA procedures. These results were verified, in saline tank studies in which the distance between the dipole due to the catheter tip and the dipole due to the target site was found to be 2.66 ± 0.52 mm. In conclusion, our algorithm to estimate the SEMD parameters from body surface potentials can potentially be a useful method to rapidly and accurately guide the catheter tip to the arrhythmic site during an RCA procedure.     

Processivity factor of KSHV contains a nuclear localization signal and binding domains for transporting viral DNA polymerase into the nucleus

Kaposi's sarcoma-associated human herpesvirus (KSHV) encodes a processivity factor (PF-8, ORF59) that forms homodimers and binds to viral DNA polymerase (Pol-8, ORF9). PF-8 is essential for stabilizing Pol-8 on template DNA so that Pol-8 can incorporate nucleotides continuously. Here, the intracellular interaction of these two viral proteins was examined by confocal immunofluorescence microscopy. When individually expressed, PF-8 was observed exclusively in the nucleus, whereas Pol-8 was found only in the cytoplasm. However, when co-expressed, Pol-8 was co-translocated with PF-8 into the nucleus. Mutational analysis revealed that PF-8 contains a nuclear localization signal (NLS) as well as domains located at the N-terminus and the C-proximal regions that are required for Pol-8 binding. This study suggests that the mechanism that enables PF-8 to transport Pol-8 into the nucleus is the first critical step required for Pol-8 and PF-8 to function processively in KSHV DNA synthesis.     

Analysis of Single Nucleotide Polymorphisms in the Gamma Block of the Major Histocompatibility Complex in Association with Clinical Outcomes of Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study

HLA haplotype mismatches have been associated with an elevated risk of acute graft-versus-host disease (aGVHD) in patients undergoing HLA-matched unrelated donor (URD) hematopoietic cell transplantation (HCT). The gamma block (GB) is located in the central MHC region between beta and delta blocks (encoding HLA-B and -C and HLA-DQ and -DR antigens, respectively) and contains numerous inflammatory and immune regulatory genes, including Bf, C2, and C4 genes. A single-center study showed that mismatches in SNPs c.2918+98G, c.3316C, and c.4385C in the GB block (C4 SNPs) were associated with higher risk of grade III-IV aGVHD. We investigated the association of GB SNP (GBS) mismatches with outcomes after 10/10 and 9/10 URD HCT (n?=?714). The primary outcome was acute GVHD. Overall survival, disease-free survival, transplantation-related mortality, relapse, chronic GVHD, and engraftment were also analyzed. DNA samples were GBS genotyped by identifying 338 SNPs across 20 kb using the Illumina NGS platform. The overall 100-day incidence of aGVHD grade II-IV and II-IV were 41% and 17%, respectively. The overall incidence of matching at all GBSs tested and at the C4 SNPs were 23% and 81%, respectively. Neither being matched across all GB SNPs tested (versus mismatched) nor having a higher number of GBS mismatches was associated with transplantation outcomes. There was no association between C4 SNP mismatches and outcomes except for an unexpected significant association between having 2 C4 SNP mismatches and a higher hazard ratio (HR) for relapse (association seen in 15 patients only; HR, 3.38, 95% confidence interval, 1.75 to 6.53; P?=?.0003). These data do not support the hypothesis that mismatching at GB is associated with outcomes after HCT.     

Some biochemical and biophysical parameters for the study of the pathogenesis of osteoarthritis: a comparison between the processes of ageing and degeneration in human hip cartilage

We have investigated the changes in some of the biochemical and biophysical properties of human femoral head cartilage on the one hand during ageing and on the other hand in osteoarthritis. Topographical variations were also investigated. The parameters studied were those relevant to cartilage function, viz., proteoglycan concentration (as expressed by the concentration of negatively charged groups), the rate of glycosaminoglycan synthesis, water content, osmotic pressure and fluid loss during compression. During ageing the fixed charge density was found to increase at all sites of the femoral head provided fibrillation was absent: osmotic pressure increased accordingly whilst loss of fluid under the effect of externally applied compression diminished. In cartilage from osteoarthritic joints the opposite changes were found. The rate of GAG synthesis varied considerably with site on the femoral head. It decreased somewhat with age on the superior surface, but increased on the inferior surface. When the same sites were compared, the rate of GAG synthesis in cartilage from osteoarthritic heads was either the same as or lower than in cartilage form normal heads in the same group.     

Serological Biomarkers and Indices for the Current Activity and Prognosis of ANCA-Associated Vasculitis: Experience in a Single Centre in Korea

Small vessel vasculitis is composed of two types of vasculitis based on immune-complex deposits, immune-complex vasculitis and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) according to the 2012 Chapel Hill Consensus Conferences Nomenclature of Vasculitis. In general, the current disease-states are assessed in three ways in real clinical practice such as activity, damage and functional status. Birmingham vasculitis activity score (BVAS, version 3) and five-factor score were calculated for assessing the cross-sectional activity and for predicting the prognosis of AAV, respectively. Since BVAS includes a wide spectrum of nine systemic items with differently weighted scores based on new-onset/worsening or persistent each symptom, it has been considered as the most reliable tool to assess AAV activity to date. However, since BVAS represents both cross-sectional and chronic clinical features, it has a limitation in flexibly reflecting the cross-sectional activity or severity of AAV. In addition, the heterogeneous items of BVAS are difficult to reflect the close correlation between BVAS and AAV pathogenesis. It is practically difficult to discover new biomarkers or indices that exceed the reliability of AAV-specific indices or acute-phase reactants established by long clinical experience. However, efforts to discover and develop new biomarkers or indices are expected to complement the clinical unmet need of existing AAV-specific indices and acute-phase reactants. In this review, we reviewed the serological biomarkers and indices that have been reported to date and introduced studies that investigated serological biomarkers and indices in Korean patients with AAV.     

A model for compound action potentials and currents in a nerve bundle II: A sensitivity analysis of model parameters for the forward and inverse calculations

We present a detailed analysis of the sensitivity of simulated Compound Action Current (CAC) and Compound Action Potential (CAP) recordings to specific model parameters, including the Single Fiber Action Currents (SFACs) and Single Fiber Action Potentials (SFAPs) that represent the contributions of each axon in the nerve bundle. In the preceding paper, we described a general method for simulating CACs and CAPs. This method uses a volume conduction model that incorporates the effects of the nerve bundle and other anisotropic properties of the region of the bundle that surrounds an individual nerve axon. In this paper, we present a complete analysis of the effects of incorrectly assigned model parameters on the simulated CAC and CAP. We also investigate the effects of incorrectly assigned parameters, recording noise, and data smoothing on the Conduction Velocity Distributions (CVDs) predicted from the CAC and CAP. We find that the simulated CAC is less sensitive to most of the parameters than is the CAP.