EEG effective connectivity during the first year of life mirrors brain synaptogenesis, myelination, and early right hemisphere predominance.

INTRODUCTION: The maturation of electroencephalogram (EEG) effective connectivity in healthy infants during the first year of life is described. METHODS: Participants: A cross-sectional sample of 125 healthy at-term infants, from 0 to 12 months of age, underwent EEG in a state of quiet sleep. PROCEDURES: The EEG primary currents at the source were described with the sLoreta method. An unmixing algorithm was applied to reduce the leakage, and the isolated effective coherence, a direct and directed measurement of information flow, was calculated. RESULTS AND DISCUSSION: Initially, the highest indices of connectivity are at the subcortical nuclei, continuing to the parietal lobe, predominantly the right hemisphere, then expanding to temporal, occipital, and finally the frontal areas, which is consistent with the myelination process. Age-related connectivity changes were mostly long-range and bilateral. Connections increased with age, mainly in the right hemisphere, while they mainly decreased in the left hemisphere. Increased connectivity from 20 to 30 Hz, mostly at the right hemisphere. These findings were consistent with right hemisphere predominance during the first three years of life. Theta and alpha connections showed the greatest changes with age. Strong connectivity was found between the parietal, temporal, and occipital regions to the frontal lobes, responsible for executive functions and consistent with behavioral development during the first year. The thalamus exchanges information bidirectionally with all cortical regions and frequency bands. CONCLUSIONS: The maturation of EEG connectivity during the first year in healthy infants is very consistent with synaptogenesis, reductions in synaptogenesis, myelination, and functional and behavioral development.

Unmixing EEG Inverse Solutions Based on Brain Segmentation.

Due to its low resolution, any EEG inverse solution provides a source estimate at each voxel that is a mixture of the true source values over all the voxels of the brain. This mixing effect usually causes notable distortion in estimates of source connectivity based on inverse solutions. To lessen this shortcoming, an unmixing approach is introduced for EEG inverse solutions based on piecewise approximation of the unknown source by means of a brain segmentation formed by specified Regions of Interests (ROIs). The approach is general and flexible enough to be applied to any inverse solution with any specified family of ROIs, including point, surface and 3D brain regions. Two of its variants are elaborated in detail: arbitrary piecewise constant sources over arbitrary regions and sources with piecewise constant intensity of known direction over cortex surface regions. Numerically, the approach requires just solving a system of linear equations. Bounds for the error of unmixed estimates are also given. Furthermore, insights on the advantages and of variants of this approach for connectivity analysis are discussed through a variety of designed simulated examples.

Assessing direct paths of intracortical causal information flow of oscillatory activity with the isolated effective coherence (iCoh).

Functional connectivity is of central importance in understanding brain function. For this purpose, multiple time series of electric cortical activity can be used for assessing the properties of a network: the strength, directionality, and spectral characteristics (i.e., which oscillations are preferentially transmitted) of the connections. The partial directed coherence (PDC) of Baccala and Sameshima (2001) is a widely used method for this problem. The three aims of this study are: (1) To show that the PDC can misrepresent the frequency response under plausible realistic conditions, thus defeating the main purpose for which the measure was developed; (2) To provide a solution to this problem, namely the "isolated effective coherence" (iCoh), which consists of estimating the partial coherence under a multivariate autoregressive model, followed by setting all irrelevant associations to zero, other than the particular directional association of interest; and (3) To show that adequate iCoh estimators can be obtained from non-invasively computed cortical signals based on exact low resolution electromagnetic tomography (eLORETA) applied to scalp EEG recordings. To illustrate the severity of the problem with the PDC, and the solution achieved by the iCoh, three examples are given, based on: (1) Simulated time series with known dynamics; (2) Simulated cortical sources with known dynamics, used for generating EEG recordings, which are then used for estimating (with eLORETA) the source signals for the final connectivity assessment; and (3) EEG recordings in rats. Lastly, real human recordings are analyzed, where the iCoh between six cortical regions of interest are calculated and compared under eyes open and closed conditions, using 61-channel EEG recordings from 109 subjects. During eyes closed, the posterior cingulate sends alpha activity to all other regions. During eyes open, the anterior cingulate sends theta-alpha activity to other frontal regions.

A maximum linear separation criterion for the analysis of neurophysiological data.

In this paper we propose an approach for the extraction of features that differentiate two populations or two experimental conditions in a neurophysiological experiment. These features consist of summarizing variables defined as total activity (e.g., total normalized log-power), computed over sets of sites in a discrete domain, such as the time-frequency-topography space. These sets are obtained as those that maximize the linear separation between the two populations, and the corresponding maps provide information that may complement that obtained by standard procedures, such as statistical parametric mapping. It is shown experimentally, using both simulated and real data, that the proposed approach may provide useful information even when the standard procedures fail, due to the conservative nature of the multiple comparison correction that must be applied in the later case.

Morphology-based hypothesis testing in discrete random fields: a non-parametric method to address the multiple-comparison problem in neuroimaging.

A new method for detecting activations in random fields, which may be useful for addressing the issue of multiple comparisons in neuroimaging, is presented. This method is based on some constructs of mathematical morphology--specifically, morphological erosions and dilations--that enable the detection of active regions in random fields possessing moderate activation levels and relatively large spatial extension, which may not be detected by the standard methods that control the family-wise error rate. The method presented here permits an appropriate control of the false positive errors, without having to adjust any threshold values, other than the significance level. The method is easily adapted to permutation-based procedures (with the usual restrictions), and therefore does not require strong assumptions about the distribution and spatio-temporal correlation structure of the data. Some examples of applications to synthetic data, including realistic fMRI simulations, as well as to real fMRI and electroencephalographic data are presented, illustrating the power of the presented technique. Comparisons with other methods that combine voxel intensity and cluster size, as well as some extensions of the method presented here based on their basic ideas are presented as well.

Morphology-based hypothesis testing in discrete random fields: a non-parametric method to address the multiple-comparison problem in neuroimaging.

A new method for detecting activations in random fields, which may be useful for addressing the issue of multiple comparisons in neuroimaging, is presented. This method is based on some constructs of mathematical morphology - specifically, morphological erosions and dilations - that enable the detection of active regions in random fields possessing moderate activation levels and relatively large spatial extension, which may not be detected by the standard methods that control the family-wise error rate. The method presented here permits an appropriate control of the false positive errors, without having to adjust any threshold values, other than the significance level. The method is easily adapted to permutation-based procedures (with the usual restrictions), and therefore does not require strong assumptions about the distribution and spatio-temporal correlation structure of the data. Some examples of applications to synthetic data, including realistic fMRI simulations, as well as to real fMRI and electroencephalographic data are presented, illustrating the power of the presented technique. Comparisons with other methods that combine voxel intensity and cluster size, as well as some extensions of the method presented here based on their basic ideas are presented as well.

Support vector regression for functional data in multivariate calibration problems.

Quantitative analyses involving instrumental signals, such as chromatograms, NIR, and MIR spectra have been successfully applied nowadays for the solution of important chemical tasks. Multivariate calibration is very useful for such purposes and the commonly used methods in chemometrics consider each sample spectrum as a sequence of discrete data points. An alternative way to analyze spectral data is to consider each sample as a function, in which a functional data is obtained. Concerning regression, some linear and nonparametric regression methods have been generalized to functional data. This paper proposes the use of the recently introduced method, support vector regression for functional data (FDA-SVR) for the solution of linear and nonlinear multivariate calibration problems. Three different spectral datasets were analyzed and a comparative study was carried out to test its performance with respect to some traditional calibration methods used in chemometrics such as PLS, SVR and LS-SVR. The satisfactory results obtained with FDA-SVR suggest that it can be an effective and promising tool for multivariate calibration tasks.