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Mediation analysis assesses whether an exposure directly produces changes in cognitive behavior or is influenced by intermediate "mediators". Electroencephalographic (EEG) spectral measurements have been previously used as effective mediators representing diverse aspects of brain function. However, it has been necessary to collapse EEG measures onto a single scalar using standard mediation methods. In this article, we overcome this limitation and examine EEG frequency-resolved functional connectivity measures as a mediator using the full EEG cross-spectral tensor (CST). Since CST samples do not exist in Euclidean space but in the Riemannian manifold of positive-definite tensors, we transform the problem, allowing for the use of classic multivariate statistics. Toward this end, we map the data from the original manifold space to the Euclidean tangent space, eliminating redundant information to conform to a "compressed CST." The resulting object is a matrix with rows corresponding to frequencies and columns to cross spectra between channels. We have developed a novel matrix mediation approach that leverages a nuclear norm regularization to determine the matrix-valued regression parameters. Furthermore, we introduced a global test for the overall CST mediation and a test to determine specific channels and frequencies driving the mediation. We validated the method through simulations and applied it to our well-studied 50+-year Barbados Nutrition Study dataset by comparing EEGs collected in school-age children (5-11 years) who were malnourished in the first year of life with those of healthy classmate controls. We hypothesized that the CST mediates the effect of malnutrition on cognitive performance. We can now explicitly pinpoint the frequencies (delta, theta, alpha, and beta bands) and regions (frontal, central, and occipital) in which functional connectivity was altered in previously malnourished children, an improvement to prior studies. Understanding the specific networks impacted by a history of postnatal malnutrition could pave the way for developing more targeted and personalized therapeutic interventions. Our methods offer a versatile framework applicable to mediation studies encompassing matrix and Hermitian 3D tensor mediators alongside scalar exposures and outcomes, facilitating comprehensive analyses across diverse research domains.
Assuntos
Eletroencefalografia , Humanos , Eletroencefalografia/métodos , Criança , Pré-Escolar , Feminino , Masculino , Conectoma/métodos , Cognição/fisiologia , Desnutrição/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/fisiologia , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , LactenteRESUMO
This paper extends frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. (i) Create lifespan Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control, developmental equations for the mean and standard deviation of qEEG traditional and Riemannian DPs were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. (ii) We also show that harmonized Riemannian norms produce z-scores with increased diagnostic accuracy predicting brain dysfunction produced by malnutrition in the first year of life and detecting COVID induced brain dysfunction. (iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings.
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Encefalopatias , COVID-19 , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Eletroencefalografia/métodos , HumanosRESUMO
We present CiftiStorm, an electrophysiological source imaging (ESI) pipeline incorporating recently developed methods to improve forward and inverse solutions. The CiftiStorm pipeline produces Human Connectome Project (HCP) and megconnectome-compliant outputs from dataset inputs with varying degrees of spatial resolution. The input data can range from low-sensor-density electroencephalogram (EEG) or magnetoencephalogram (MEG) recordings without structural magnetic resonance imaging (sMRI) to high-density EEG/MEG recordings with an HCP multimodal sMRI compliant protocol. CiftiStorm introduces a numerical quality control of the lead field and geometrical corrections to the head and source models for forward modeling. For the inverse modeling, we present a Bayesian estimation of the cross-spectrum of sources based on multiple priors. We facilitate ESI in the T1w/FSAverage32k high-resolution space obtained from individual sMRI. We validate this feature by comparing CiftiStorm outputs for EEG and MRI data from the Cuban Human Brain Mapping Project (CHBMP) acquired with technologies a decade before the HCP MEG and MRI standardized dataset.
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Analysis of joint motion data (AJMD) by Kinect, such as velocity, has been widely used in many research fields, many of which focused on how one joint moves with another, namely bivariate AJMD. However, these studies might not accurately reflect the motor symptoms in patients. The human body can be divided into six widely accepted parts (head, trunk and four limbs), which are interrelated and interact with each other. Therefore, in this study we attempted to investigate how the major joints of one body part move with the ones in another body part, namely multivariate AJMD. For method illustration, the motion data of sit-to-stand-to-sit for healthy participants and people with Parkinson disease (PD) were employed. Four types of multivariate AJMD were investigated by eigenspace-maximal-information-canonical-correlation-analysis, which obtained maximal- information-eigen-coefficients (MIECes), the parameters for quantifying the correlation between two sets of joints located in two different body parts. The results show that healthy participants have significantly higher MIECes than the PD patients (p-value < 0.0001). Furthermore, the area under the receiver operating characteristic curve value for the classification between healthy participants and PD patients reaches up to 1.00. In conclusion, we demonstrated the possibility of using multivariate AJMD for motion feature extraction, which may be helpful for medical research and engineering.
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Algoritmos , Articulações/fisiopatologia , Doença de Parkinson/fisiopatologia , Adulto , Idoso , Fenômenos Biomecânicos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Análise Multivariada , Curva ROC , Postura Sentada , Posição OrtostáticaRESUMO
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.