A serial functional connectivity MRI study in healthy individuals assessing the variability of connectivity measures: reduced interhemispheric connectivity in the motor network during continuous performance

To date, little data is available on the reproducibility of functional connectivity MRI (fcMRI) studies. Here, we tested the variability and reproducibility of both the functional connectivity itself and different statistical methods to analyze this phenomenon. In the main part of our study, we repeatedly examined two healthy subjects in 10 sessions over 6 months with fcMRI. Cortical areas involved in motor function were examined under two different cognitive states: during continuous performance (CP) of a flexion/extension task of the fingers of the right hand and while subjects were at rest. Connectivity to left primary motor cortex (lSM1) was calculated by correlation analysis. The resulting correlation coefficients were transformed to z-scores of the standard normal distribution. For each subject, multisession statistical analyses were carried out with the z-score maps of the resting state (RS) and the CP experiments. First, voxel based t tests between the two groups of fcMRI experiments were performed. Second, ROI analyses were carried out for contralateral right SM1 and for supplementary motor area (SMA). For both ROI, mean and maximum z-score were calculated for each experiment. Also, the fraction of significantly (P<.05) correlated voxels (FCV) in each ROI was calculated. To evaluate the differences between the RS and the CP condition, paired t tests were performed for the mean and maximum z-scores, and Wilcoxon signed ranks tests for matched pairs were carried out for the FCV. All statistical methods and connectivity measures under investigation yielded a distinct loss in left–right SM1 connectivity under the CP condition. For SMA, interindividual differences were apparent. We therefore repeated the fcMRI experiments and the ROI analyses in a group of seven healthy subjects (including the two subjects of the main study). In this substudy, we were able to verify the reduction of left–right SM1 connectivity during unilateral performance. Still, the direction of SMA to lSM1 connectivity change during the CP condition remained undefined as four subjects showed a connectivity increase and three showed a decrease. In summary, we were able to demonstrate a distinct reduction in left–right SM1 synchrony in the CP condition compared to the RS both in the longitudinal and in the multisubject study. This effect was reproducible with all statistical methods and all measures of connectivity under investigation. We conclude that despite intra- and interindividual variability, serial and cross-sectional assessment of functional connectivity reveals stable and reliable results.     

Quantitative cerebral magnetic resonance imaging during ACTH treatment of multiple sclerosis

Serial MR scans were performed with the 2DFT imaging method and the filtered backprojection imaging method on 12 patients with multiple sclerosis in acute phase, 4 in a relapsing/remitting form, and 8 in a progressive form, before, during and after ACTH treatment. Both T₁ and T_2mono relaxation times, obtained by fitting transverse magnetization decay curves with a monoexponential function within the apparently normal white matter and the areas of increased signal, were measured. With the backprojection method it was possible to fit the transverse magnetization decay curve with a biexponential function and obtain T_2long and T_2short relaxation times. The T_2mono and T₁ relaxation times of the apparently normal white matter were significantly different from those obtained for volunteers, but no significant differences were found before, during, or after treatment. The transverse magnetization decay curves of the areas of increased signal were better fitted by a biexponential function. No significant changes in these relaxation times were observed after ACTH treatment. These results argue against an anti-oedematous action of ACTH and may suggest that it has an immunosuppressant effect.     

Low-frequency signal changes reflect differences in functional connectivity between good readers and dyslexics during continuous phoneme mapping

The current fMRI study investigated correlations of low-frequency signal changes in the left inferior frontal gyrus, right inferior frontal gyrus and cerebellum in 13 adult dyslexic and 10 normal readers to examine functional networks associated with these regions. The extent of these networks to regions associated with phonological processing (frontal gyrus, occipital gyrus, angular gyrus, inferior temporal gyrus, fusiform gyrus, supramarginal gyrus and cerebellum) was compared between good and dyslexic readers. Analysis of correlations in low-frequency range showed that regions known to activate during an "on-off" phoneme-mapping task exhibit synchronous signal changes when the task is administered continuously (without any "off" periods). Results showed that three functional networks, which were defined on the basis of documented structural deficits in dyslexics and included regions associated with phonological processing, differed significantly in spatial extent between good readers and dyslexics. The methodological, theoretical and clinical significance of the findings for advancing fMRI research and knowledge of dyslexia are discussed.     

Origin of network connectivity and structural units in amorphous SiSe2

We elucidate the structural properties of amorphous SiSe2 by first-principles molecular dynamics. The calculated structure factor is in very good agreement with experiments, as well as the number of corner- and edge-sharing tetrahedra. By focusing on the sequences of Si atoms linked via intra- and intertetrahedral bonds, we identify the predominant structural motifs. The sequences involving both corner- and edge-sharing connections are significantly more frequent than those formed exclusively by edge-shared Si atoms. Our results clarify a longstanding controversy on the structure of this prototypical disordered network-forming material.     

静息态脑电信号动态功能连接分析

静息态脑功能连接分析是近年来脑研究的一个热点问题, 对于某些脑疾病的诊断及成因理解具有重要意义. 已有的脑功能连接研究基本上都假设功能连接网络在一段时间内是稳定不变的, 但越来越多的证据表明它应该是随时间动态变化的. 对25名被试睁眼和闭眼状态的64电极脑电生理信号, 采用独立成分分析、滑动时间窗、低分辨率脑电断层溯源、图论等方法和技术进行动态功能连接分析, 展现了睁眼和闭眼两种基线状态下视觉网络、默认网络等功能连接网络随时间的动态变化, 并对动态连接矩阵进行主成分分析得到了在整个时间段内具有代表意义的功能连接模式. 该结论支持和补充了传统稳态脑功能连接的研究, 也将为相关实验设计以及脑电信号临床研究提供基线选择依据.     

Changes in the acoustics of the Moscow Conservatory Great Hall two years after reconstruction

We present the results of measuring the reverberation time of the Moscow Conservatory Great Hall. Measurements were conducted with a half-year interval over two years after completion of reconstruction. It is demonstrated that the changes in reverberation time at low and middle frequencies are barely distinguishable to subjective perception, and at high frequencies, significant fluctuations are observed, related to seasonal changes in the climatic conditons.     

Estimation of the effective and functional human cortical connectivity with structural equation modeling and directed transfer function applied to high-resolution EEG

Different brain imaging devices are presently available to provide images of the human functional cortical activity, based on hemodynamic, metabolic or electromagnetic measurements. However, static images of brain regions activated during particular tasks do not convey the information of how these regions are interconnected. The concept of brain connectivity plays a central role in the neuroscience, and different definitions of connectivity, functional and effective, have been adopted in literature. While the functional connectivity is defined as the temporal coherence among the activities of different brain areas, the effective connectivity is defined as the simplest brain circuit that would produce the same temporal relationship as observed experimentally among cortical sites. The structural equation modeling (SEM) is the most used method to estimate effective connectivity in neuroscience, and its typical application is on data related to brain hemodynamic behavior tested by functional magnetic resonance imaging (fMRI), whereas the directed transfer function (DTF) method is a frequency-domain approach based on both a multivariate autoregressive (MVAR) modeling of time series and on the concept of Granger causality.

This study presents advanced methods for the estimation of cortical connectivity by applying SEM and DTF on the cortical signals estimated from high-resolution electroencephalography (EEG) recordings, since these signals exhibit a higher spatial resolution than conventional cerebral electromagnetic measures. To estimate correctly the cortical signals, we used a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from individual MRI, a distributed source model and a regularized linear inverse source estimates of cortical current density. Before the application of SEM and DTF methodology to the cortical waveforms estimated from high-resolution EEG data, we performed a simulation study, in which different main factors (signal-to-noise ratio, SNR, and simulated cortical activity duration, LENGTH) were systematically manipulated in the generation of test signals, and the errors in the estimated connectivity were evaluated by the analysis of variance (ANOVA). The statistical analysis returned that during simulations, both SEM and DTF estimators were able to correctly estimate the imposed connectivity patterns under reasonable operative conditions, that is, when data exhibit an SNR of at least 3 and a LENGTH of at least 75 s of nonconsecutive EEG recordings at 64 Hz of sampling rate.

Hence, effective and functional connectivity patterns of cortical activity can be effectively estimated under general conditions met in any practical EEG recordings, by combining high-resolution EEG techniques and linear inverse estimation with SEM or DTF methods. We conclude that the estimation of cortical connectivity can be performed not only with hemodynamic measurements, but also with EEG signals treated with advanced computational techniques.     

Differential cognitive impairment for diverse forms of multiple sclerosis

Background  

Cognitive impairment is a common feature in multiple sclerosis (MS) patients and occurs in 60% of all cases. Unfortunately, neurological examination does not always agree with the neuropsychological evaluation in determining the cognitive profile of the patient. On the other hand, psychophysiological techniques such as event-related potentials (ERPs) can help in evaluating cognitive impairment in different pathologies.     

Vocal fundamental frequency characteristics during the first two years of life

Vocal fundamental frequency (Fo) characteristics were sampled for a group of seven young children. The children were followed longitudinally for a 12-month period, spanning preword, single-word, and multiword vocalizations. The Fo characteristics were analyzed with reference to chronological age, vocalization length, and lexicon size. Measures of average Fo and Fo variability changed little during the 12-month period for each child. A rising-falling intonation contour was the most prevalent Fo contour among the children. In general, the influence of vocalization length and language acquisition on measures of Fo was negligible. It is suggested that relative uniformity in vocal Fo exists in early vocalizations across preword and meaningful speech periods.     

Acoustic analysis of voice in multiple sclerosis patients

The objective is to investigate the presence of dysphonic symptoms in multiple sclerosis (MS) patients and to compare quantitative acoustic parameters in multiple sclerosis patients and normal individuals. The method of study was an 8-month controlled cross-sectional that was carried out with 106 individuals (30 MS, 76 controls). Both groups included males and females from 20 to 55 years. Exclusion criteria were prior vocal disorder, laryngeal microsurgery, recent endotracheal intubation, tumors, laryngeal, lung or mediastinal metastases, respiratory disease, and other associated neurological diagnoses. For dysphonic symptoms (qualitative variables), associations were assessed using Mantel-Haenszel's chi2 test, with Yates correction or the Fisher exact test when necessary. Statistical significance was set at p< or =0.05. Dysphonia was observed in 70% of MS individuals versus 33% of controls (p=0.01). Association was found between MS and dysphonia (OR: 2.2, CI 95%: 1.13-4.25). Fundamental frequency was higher among MS patients (p=0.01). Fundamental frequency deviation was significantly higher in MS women (but not men) than controls (p=0.00). Jitter was higher in MS men than in all other groups (p=0.00). Results suggest that evaluation and treatment of MS patients should be revised, evaluating voice alterations in relation to other signs. MS seems to intensify gender effect on fundamental frequency deviation, noise, and jitter, with MS women presenting fewer voice variations than men.     

Cross-frequency network analysis of functional brain connectivity in temporal lobe epilepsy

In this study, we investigate the cross-frequency coupling and functional brain networks in the subjects with temporal lobe epilepsy(TLE) using interictal EEG signals. The phase to phase synchronization within and across frequency bands is calculated and a significant difference between the epilepsy and control groups is observed. Compared with the controls,the epilepsy patients exhibit a stronger within-frequency coupling(WFC) within theta and beta bands, and shows a stronger cross-frequency coupling(CFC) in the delta–alpha and theta–alpha band pairs, but a weakened CFC in alpha–beta band pairs. The weakened coupling between alpha and high frequency band reflects a suppression of phase modulation between the brain regions related to epilepsy. Moreover, WFC and CFC are positively correlated, which is higher in the patients relative to controls. We further reconstruct functional brain connectivity and find that both WFC and CFC networks show small-world properties. For the epilepsy, the small-world efficiency is enhanced in the CFC networks in delta–alpha and theta–alpha band pairs, whereas weakened between alpha and beta bands, which suggests a shift away from the optimal operating point in the epileptic brain with a new balance between WFC and CFC. Our results may help us to understand the important role of information communication across different frequency bands and shed new light on the study of pathology of epilepsy.     

Images-based suppression of unwanted global signals in resting-state functional connectivity studies

Correlated fluctuations of low-frequency fMRI signal have been suggested to reflect functional connectivity among the involved regions. However, large-scale correlations are especially prone to spurious global modulations induced by coherent physiological noise. Cardiac and respiratory rhythms are the most offending component, and a tailored preprocessing is needed in order to reduce their impact. Several approaches have been proposed in the literature, generally based on the use of physiological recordings acquired during the functional scans, or on the extraction of the relevant information directly from the images. In this paper, the performances of the denoising approach based on general linear fitting of global signals of noninterest extracted from the functional scans were assessed. Results suggested that this approach is sufficiently accurate for the preprocessing of functional connectivity data.     

Partial volume effects in MRI studies of multiple sclerosis

We have estimated the accuracy of volume measurements of multiple sclerosis (MS) lesions made using magnetic resonance imaging (MRI) for lesions of comparable diameter to the image slice thickness. We used a phantom containing objects of known volume and obtained images using a range of slice thicknesses. Measurements on the phantom were used to assess a theoretical model, which was then employed to investigate the effects of image dimensions and geometry upon volume measurement accuracy. We observed measured volume to be dependent upon slice thickness. Thin slices gave the most accurate estimate of volume. As slice thickness increased relative to object diameter, the error in the volume measurement increased (to as much as 100%), the volume measured being dependent on the position of the object relative to the slice center. Using a signal intensity threshold value of 50% to outline objects gave results closest to the actual volume. As expected, a lower threshold value tended to give higher volume estimates (up to 100% larger), as did a semi-automated local edge detection technique. For accurate volume measurement, the slice thickness should be no more than a fifth of anticipated object diameter. For typical MS lesions (7 mm in diameter), this implies using a 1.5-mm slice thickness. For serial studies, a repositioning error of 1 mm could lead to differences in the volume measurement of individual lesions of up to 12% between studies for lesions of typical MS size and 5-mm slice thickness. These results emphasize the need for accurate patient repositioning, relatively thin slices, for regular quality assurance checks to ensure that pixel size and slice position are correct and stable over time, and that lesion outlining is performed in a consistent fashion. We would recommend the use of a 3D sequence with 1 mm cubic voxels for accurate measurements of MS lesions.     

Gender effect on neurodegeneration and myelin markers in an animal model for multiple sclerosis

Background  

Multiple sclerosis (MS) varies considerably in its incidence and progression in females and males. In spite of clinical evidence, relatively few studies have explored molecular mechanisms possibly involved in gender-related differences. The present study describes possible cellular- and molecular-involved markers which are differentially regulated in male and female rats and result in gender-dependent EAE evolution and progression. Attention was focused on markers of myelination (MBP and PDGFαR) and neuronal distress and/or damage (GABA synthesis enzymes, GAD65 and GAD67, NGF, BDNF and related receptors), in two CNS areas, i.e. spinal cord and cerebellum, which are respectively severely and mildly affected by inflammation and demyelination. Tissues were sampled during acute, relapse/remission and chronic phases and results were analysed by two-way ANOVA.     

Spectral pattern of total creatine and trimethyl ammonium in multiple sclerosis

Fatigue and impairment mobility are frequent problems in multiple sclerosis (MS). Despite its enormous potential, in vivo (1)H MRS of skeletal muscles for MS patients is a largely unexplored field. One fundamental question remains unanswered: whether MS can cause observable proton metabolite changes. High quality two-dimensional in vivo (1)H MRS reveals that the spectral pattern of total creatine (tCr) and trimethyl ammonium (TMA) of soleus muscles of MS patients can be distinctively different from that of healthy volunteers, and in vivo (1)H MRS of skeletal muscles has a potential to become a useful tool in MS study.     

Abnormal dynamics of cortical resting state functional connectivity in chronic headache patients

The goals of this study are to characterize the temporal dynamics of inter-regional connectivity of the brain in chronic headache (CH) patients versus their age/gender matched controls (CON_CH, n = 28 pairs), and to determine whether dynamic measures reveal additional features to static functional connectivity and correlate with psychometric scores. Cortical thickness and inter-regional resting state fMRI connectivity were quantified and compared between CH and CON_CH groups. Six cortical regions of interest (ROI) pairs that exhibited correlated cortical thickness and static functional connectivity abnormalities were selected for temporal dynamic analysis. Two methods were used: temporal sliding-window (SW) and wavelet transformation coherence (WTC). SW analyses using three temporal windows of 30, 60, 120 s revealed that all six ROI pairs of CH exhibited higher percentage of strong connectivity (high r values), and smaller fast Fourier transform (FFT) amplitudes at a very low frequency range (i.e., 0.002–0.01 Hz), compared to those of CON_CH. These features were particularly prevalent in the 120 s window analysis. Less variable dynamic fluctuation (i.e., smaller standard deviation of r values) was identified in two out of six ROI pairs in CH. WTC analysis revealed that time-averaged coherence was generally greater in CH than CON_CH between wavelet decomposition scales 20 to 55 (0.018–0.05 Hz), and was statistically significant in three out of six ROI pairs. Together, the most robust and significant differences in temporal dynamics between CH and CON_CH were detected in two ROI pairs: left medial-orbitofrontal–left posterior-cingulate and left medial-orbitofrontal–left inferior-temporal. The high degrees of sleep disturbance (high PSQI score), depression (high HRSD score) and fatigue (low SF-36 score) were associated with high degree of inter-regional temporal coherence in CH. In summary, these dynamic functional connectivity (dFC) measures uncovered a temporal “lock-down” condition in a subset of ROI pairs, showing static functional connectivity changes in CH patients. This study provides important evidence for the presence of associated psychological wellbeing and abnormal temporal dynamics in between specific cortical regions in CH patients.     

Comparison of the small-world topology between anatomical and functional connectivity in the human brain

We applied graph analysis to both anatomical and functional connectivity in the human brain. Anatomical connectivity was acquired from diffusion tensor imaging data by probabilistic fiber tracking, and functional connectivity was extracted from resting-state functional magnetic resonance imaging data by calculating correlation maps of time series. For the same subject, anatomical networks seemed to be disassortative, while functional networks were significantly assortative. Anatomical networks showed higher efficiency and smaller diameters than functional networks. It can be proposed that anatomical connectivity, as a major constraint of functional connectivity, has a relatively stable and efficient structure to support functional connectivity that is more changeable and flexible.     

Density functional theory study of structural stability for gas hydrate

Using the first-principles method based on the density functional theory(DFT),the structures and electronic properties of different gas hydrates(CO_2,CO,CH_4,and H_2) are investigated within the generalized gradient approximation.The structural stability of methane hydrate is studied in this paper.The results show that the carbon dioxide hydrate is more stable than the other three gas hydrates and its binding energy is-2.36 e V,and that the hydrogen hydrate is less stable and the binding energy is-0.36 e V.Water cages experience repulsion from inner gas molecules,which makes the hydrate structure more stable.Comparing the electronic properties of two kinds of water cages,the energy region of the hydrate with methane is low and the peak is close to the left,indicating that the existence of methane increases the stability of the hydrate structure.Comparing the methane molecule in water cages and a single methane molecule,the energy of electron distribution area of the former is low,showing that the filling of methane enhances the stability of hydrate structure.     

Non-local density functional theory for the electronic and structural properties of semiconductors

Calculations have been carried out within the density functional formalism using an exchange-correlation functional with explicit nonlocal dependence on the charge density. The functional includes the effects of the qualitatively different screening in a semiconductor due to the gap in the spectrum. For the test cases of Si and Ge, substantial improvement is found for the minimum gap. The structural properties are in excellent agreement with experiment.     

Detecting functional connectivity in the resting brain: a comparison between ICA and CCA

Independent component analysis (ICA) and cross-correlation analysis (CCA) are general tools for detecting resting-state functional connectivity. In this study, we jointly evaluated these two approaches based on simulated data and in vivo functional magnetic resonance imaging data acquired from 10 resting healthy subjects. The influence of the number of independent components (maps) on the results of ICA was investigated. The influence of the selection of the seeds on the results of CCA was also examined. Our results reveal that significant differences between these two approaches exist. The performance of ICA is superior as compared with that of CCA; in addition, the performance of ICA is not significantly affected by structured noise over a relatively large range. The results of ICA could be affected by the number of independent components if this number is too small, however. Converting the spatially independent maps of ICA into z maps for thresholding tends to overestimate the false-positive rate. However, the overestimation is not very severe and may be acceptable in most cases. The results of CCA are dependent on seeds location. Seeds selected based on different criteria will significantly affect connectivity maps.