Estimation Of Brain Connectivity Research Articles

Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

Similarity between structural and proxy estimates of brain connectivity

Functional magnetic resonance and diffusion weighted imaging have so far made a major contribution to delineation of the brain connectome at the macroscale. While functional connectivity (FC) was shown to be related to structural connectivity (SC) to a certain degree, their spatial overlap is unknown. Even less clear are relations of SC with estimates of connectivity from inter-subject covariance of regional F18-fluorodeoxyglucose uptake (FDGcov) and grey matter volume (GMVcov). Here, we asked to what extent SC underlies three proxy estimates of brain connectivity: FC, FDGcov and GMVcov. Simultaneous PET/MR acquisitions were performed in 56 healthy middle-aged individuals. Similarity between four networks was assessed using Spearman correlation and convergence ratio (CR), a measure of spatial overlap. Spearman correlation coefficient was 0.27 for SC-FC, 0.40 for SC-FDGcov, and 0.15 for SC-GMVcov. Mean CRs were 51% for SC-FC, 48% for SC-FDGcov, and 37% for SC-GMVcov. These results proved to be reproducible and robust against image processing steps. In sum, we found a relevant similarity of SC with FC and FDGcov, while GMVcov consistently showed the weakest similarity. These findings indicate that white matter tracts underlie FDGcov to a similar degree as FC, supporting FDGcov as estimate of functional brain connectivity.

Brain Connectivity Estimation Pitfall in Multiple Trials of Electroencephalography Data.

The electroencephalography signal is well suited to calculate brain connectivity due to its high temporal resolution. When the purpose is to compute connectivity from multi-trial electroencephalography (EEG) data, confusion arises about how these trials involved in calculating the connectivity. The purpose of this paper is to study this confusing issue using simulated and experimental data. To this end, Granger causality-based connectivity measures were considered. Using simulations, two signals were generated with known AR (auto-regressive) coefficients and then simple multivariate autoregressive (MVAR) models based on different numbers of trials were extracted. For accurate estimation of the MVAR model, the data samples should be sufficient. Two Granger causality-based connectivity, granger causality (GC) and Partial directed coherence (PDC) were estimated. Estimating connectivity corresponding to small trial numbers (5 and 10 trials) resulted in an average value of connectivity that is significantly higher and also more variable over different estimates. By increasing the number of trials, the MVAR model has fitted more appropriately to the data and the connectivity values were converged. This procedure was implemented on real EEG data. The obtained results agreed well with the findings of simulated data. The results showed that the brain connectivity should calculate for each trial, and then average the connectivity values on all trials. Also, the larger the trial numbers, the MVAR model has fitted more appropriately to the data, and connectivity estimations are more reliable. The average of connectivity values on trials is considered brain connectivity.Connectivity estimations are more reliable for larger trial numbers.Estimations of connectivity for small trial numbers are not valid. Several different techniques can be utilized to evaluate brain connectivity such as functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), electroencephalography (EEG) and etc. Connectivity estimation methods are associated with computing the correspondence of neural signals over time, therefore modalities such as EEG due to their fine temporal resolution are well suited to calculate such connectivity. When the purpose is to compute connectivity from multi-trial data, confusion arises about how these trials and how many trials are involved in calculating the connectivity. During calculating brain connectivity from data with many observation epochs, the question arises whether brain connectivity is calculated for each trial and then average or for the averaged trials. The target of this paper is to study the abovementioned issue using simulated data and realistic EEG data. Our analysis indicated that the brain connectivity should calculate for each trial, and then average the connectivity values on all trials. It was also found that estimating connectivity corresponding to small trial numbers resulted in an average value of connectivity that is significantly higher and also more variable over different estimates and is not valid. These findings can help us in the correct estimation of brain connectivity.

Event-related potential and oscillatory cortical activities of artistic methodology in information visualization design in human–computer interface

Data visualization is essential for interface design in human–computer interaction. With the advances in information technology, artists and designers have used creative thoughts and artistic methodologies in information design and data visualization. We design a method that minimizes readers’ time to memorize data or information through event-related potential (ERP), electroencephalography (EEG) topography, brain connectivity, and volume source estimation analyses. We developed four information visualization interfaces by importing career data from the World Bank Data: integrated generative artistic design (IGAD), separated generative artistic design (SGAD), integrated line chart design (ILCD), and separated line chart design (SLCD). We then compared subjective evaluations and brain electrophysiological biofeedback on user experience (UX) with the aesthetics and usability of user interface design. We enroled 52 healthy subjects (26 men and 26 women) for psychological or physiological differences. The line chart wireframe design and initial animation arousal were found to be more acceptable than the generative style through P200 and N200 analyses. Meanwhile, late positive complex (LPC) and subjective evaluations showed that SGAD is the most beautiful interface for information visualization design. LPC showed generative art as more appealing than the line chart in the left and middle brain regions from the frontal-to-central lobes. We found that decreased delta, theta, and alpha and increased gamma lead to significant memory enhancement in ILCD compared to IGAD. Men and women were found to have different relative power activations in delta, theta, alpha, and gamma. The sex-based difference in visual working memory in theta and gamma connectivity in frontal-to-central brain regions occurred in the ILCD interface design. The difference between delta activation on line chart design and theta and gamma activated in the frontal-parietal-occipital brain in SGAD helped reveal how different designs influence the same data result through connectivity analysis. Volume estimation revealed that the activations vary between brain regions across the one-minute analysis. The subjective evaluation produced different results from LPC objective evaluation aesthetic judgement but the same results in SGAD interface design. We found that memory performance decreases from SLCD, ILCD, SGAD, to IGAD. We also found that most people quickly memorized incrementing and decrementing data trends, which can help future human–computer interface and information visualization design.

Dynamic covariance estimation via predictive Wishart process with an application on brain connectivity estimation

Modeling the complex dependence in multivariate time series data is a fundamental problem in statistics and machine learning. Traditionally, the task has been approached with methods such as multivariate autoregressive models and multivariate generalized autoregressive conditional heteroskedasticity models, and Gaussian process based methods are recently becoming popular by leveraging the flexibility of non-parametric learning. However, few methods exist that directly model the dynamics of the covariance matrices except generalized Wishart process (GWP), and even the generalized Wishart process is limited with applications on small dataset due to the extremely high computational capacity induced by multiple Gaussian processes. In this regard, a novel stochastic process named as Predictive Wishart Process (PWP) is proposed, which provides a collection of positive semi-definite random matrices indexed by input variables. The PWP projects process realizations of GWP to a lower dimensional subspace to efficiently estimate every GWP. The theoretical properties of it are examined, and both Bayesian inference and efficient variational expectation maximization are explored in relation to it. Moreover, the PWP is empirically tested on synthetically generated time-series data to validate competitive reconstructive performance and efficient predictive performance, and applied on a large-scale real functional magnetic resonance imaging (fMRI) dataset from Human Connectome Project (HCP) to demonstrate its practicality. A thorough statistical analysis with visualizations is conducted on the brain connectivity, and also a PWP-based multi-task learning framework is proposed to extract meaningful features from individual fMRIs.

Efficient Estimation of Time-Dependent Brain Functional Connectivity Using Anatomical Connectivity Constraints

There is ongoing interest in the dynamics of resting state brain networks (RSNs) as potential predictors of cognitive and behavioural states. Multivariate Autoregressors (MAR) are used to model regional brain activity as a linear combination of past activity in other regions. The coefficients of the MAR are taken as estimates of effective brain connectivity. However, assumption of stationarity, and the large number of coefficients renders the MAR impractical for estimating brain networks from standard neuroimaging time-series of limited durations. We propose HsMM-MAR-AC, a novel sparse hybrid discrete-continuous model for the efficient estimation of time-dependent effective brain networks from non-stationary brain activity time-series. Discrete quasi-stationary Brain States, and the fast switching between them, are modelled by a Hidden semi-Markov Model whose continuous emissions are drawn from a sparse MAR. The coefficients of the MAR are restricted by Anatomical Brain Connectivity information in two ways: 1) Effective direct connectivity between two brain regions is only considered if the corresponding anatomical connection exists; and 2) the autoregressors lag associated with each connection is based on the fiber length between the two regions, such that only one lag per connection is estimated. We test the accuracy of HsMM-MAR-AC in recovering simulated resting state networks of various durations, and at different thresholds of anatomical restrictions. We demonstrate that HsMM-MAR-AC recovers the RSNs more accurately than the benchmark method of the sliding window, with as little as 4 minutes of data. We also show that when the anatomical restrictions are relaxed, longer time-series are needed to estimate the networks, and became computationally unfeasible without anatomical restrictions. HsMM-MAR-AC offers an efficient model for estimating time-dependent Effective Connectivity from neuroimaging data that exploits the advantages of Hidden Markov and MAR models without identifiability problems, excessive demand on data collection, or unnecessary computational effort.

Comparison of beamformer and ICA for dynamic connectivity analysis: A simultaneous MEG-SEEG study

Magnetoencephalography (MEG) is a powerful tool for estimating brain connectivity with both good spatial and temporal resolution. It is particularly helpful in epilepsy to characterize non-invasively the epileptic networks. However, using MEG to map brain networks requires solving a difficult inverse problem that introduces uncertainty in the activity localization and connectivity measures. Our goal here was to compare independent component analysis (ICA) followed by dipole source localization and the linearly constrained minimum-variance beamformer (LCMV-BF) for characterizing regions with interictal epileptic activity and their dynamic connectivity. After a simulation study, we compared ICA and LCMV-BF results with intracerebral EEG (stereotaxic EEG, SEEG) recorded simultaneously in 8 epileptic patients, which provide a unique ‘ground truth’ to which non-invasive results can be confronted. We compared the signal time courses extracted applying ICA and LCMV-BF on MEG data to that of SEEG, both for the actual signals and the dynamic connectivity computed using cross-correlation (evolution of links in time).With our simulations, we illustrated the different effect of the temporal and spatial correlation among sources on the two methods. While ICA was more affected by the temporal correlation but robust against spatial configurations, LCMV-BF showed opposite behavior. Moreover, ICA seems more suited to retrieve the simulated networks.In case of real patient data, good MEG/SEEG correlation and good localization were obtained in 6 out of 8 patients. In 4 of them ICA had the best performance (higher correlation, lower localization distance). In terms of dynamic connectivity, the evolution in time of the cross-correlation links could be retrieved in 5 patients out of 6, however, with more variable results in terms of correlation and distance. In two patients LCMV-BF had better results than ICA. In one patient the two methods showed equally good outcomes, and in the remaining two patients ICA performed best.In conclusion, our results obtained by exploiting simultaneous MEG/SEEG recordings suggest that ICA and LCMV-BF have complementary qualities for retrieving the dynamics of interictal sources and their network interactions.

Improving EEG-Based Driver Distraction Classification Using Brain Connectivity Estimators

This paper discusses a novel approach to an EEG (electroencephalogram)-based driver distraction classification by using brain connectivity estimators as features. Ten healthy volunteers with more than one year of driving experience and an average age of 24.3 participated in a virtual reality environment with two conditions, a simple math problem-solving task and a lane-keeping task to mimic the distracted driving task and a non-distracted driving task, respectively. Independent component analysis (ICA) was conducted on the selected epochs of six selected components relevant to the frontal, central, parietal, occipital, left motor, and right motor areas. Granger–Geweke causality (GGC), directed transfer function (DTF), partial directed coherence (PDC), and generalized partial directed coherence (GPDC) brain connectivity estimators were used to calculate the connectivity matrixes. These connectivity matrixes were used as features to train the support vector machine (SVM) with the radial basis function (RBF) and classify the distracted and non-distracted driving tasks. GGC, DTF, PDC, and GPDC connectivity estimators yielded the classification accuracies of 82.27%, 70.02%, 86.19%, and 80.95%, respectively. Further analysis of the PDC connectivity estimator was conducted to determine the best window to differentiate between the distracted and non-distracted driving tasks. This study suggests that the PDC connectivity estimator can yield better classification accuracy for driver distractions.

Effect of functional and effective brain connectivity in identifying vowels from articulation imagery procedures.

Articulation imagery, a form of mental imagery, refers to the activity of imagining or speaking to oneself mentally without an articulation movement. It is an effective domain of research in speech impaired neural disorders, as speech imagination has high similarity to real voice communication. This work employs electroencephalography (EEG) signals acquired from articulation and articulation imagery in identifying the vowel being imagined during different tasks. EEG signals from chosen electrodes are decomposed using the empirical mode decomposition (EMD) method into a series of intrinsic mode functions. Brain connectivity estimators and entropy measures have been computed to analyze the functional cooperation and causal dependence between different cortical regions as well as the regularity in the signals. Using machine learning techniques such as multiclass support vector machine (MSVM) and random forest (RF), the vowels have been classified. Three different training and testing protocols (Articulation-AR, Articulation imagery-AI and Articulation vs Articulation imagery-AR vs AI) were employed for identifying the vowel being imagined of articulating. An overall classification accuracy of 80% was obtained for articulation imagery protocol which was found to be higher than the other two protocols. Also, MSVM techniques outperformed the RF technique in terms of the classification accuracy. The effect of brain connectivity estimators and machine learning techniques seems to be reliable in identifying the vowel from the subjects' thought and thereby assisting the people with speech impairment.

Granger Causality Inference in EEG Source Connectivity Analysis: A State-Space Approach.

This article addresses the problem of estimating brain effective connectivity from electroencephalogram (EEG) signals using a Granger causality (GC) characterized on state-space models, extended from the conventional vector autoregressive (VAR) process. The scheme involves two main steps: model estimation and model inference to estimate brain connectivity. The model estimation performs a subspace identification and active source selection based on group-norm regularized least-squares. The model inference relies on the concept of state-space GC that requires solving a Riccati equation for the covariance of estimation error. We verify the performance on simulated datasets that represent realistic human brain activities under several conditions, including percentages and location of active sources, and the number of EEG electrodes. Our model's accuracy in estimating connectivity is compared with a two-stage approach using source reconstructions and a VAR-based Granger analysis. Our method achieved better performances than the two-stage approach under the assumptions that the true source dynamics are sparse and generated from state-space models. When the method was applied to a real EEG SSVEP dataset, the temporal lobe was found to be a mediating connection between the temporal and occipital areas, which agreed with findings in previous studies.

Maximum entropy models provide functional connectivity estimates in neural networks

Tools to estimate brain connectivity offer the potential to enhance our understanding of brain functioning. The behavior of neuronal networks, including functional connectivity and induced connectivity changes by external stimuli, can be studied using models of cultured neurons. Cultured neurons tend to be active in groups, and pairs of neurons are said to be functionally connected when their firing patterns show significant synchronicity. Methods to infer functional connections are often based on pair-wise cross-correlation between activity patterns of (small groups of) neurons. However, these methods are not very sensitive to detect inhibitory connections, and they were not designed for use during stimulation. Maximum Entropy (MaxEnt) models may provide a conceptually different method to infer functional connectivity. They have the potential benefit to estimate functional connectivity during stimulation, and to infer excitatory as well as inhibitory connections. MaxEnt models do not involve pairwise comparison, but aim to capture probability distributions of sets of neurons that are synchronously active in discrete time bins. We used electrophysiological recordings from in vitro neuronal cultures on micro electrode arrays to investigate the ability of MaxEnt models to infer functional connectivity. Connectivity estimates provided by MaxEnt models correlated well with those obtained by conditional firing probabilities (CFP), an established cross-correlation based method. In addition, stimulus-induced connectivity changes were detected by MaxEnt models, and were of the same magnitude as those detected by CFP. Thus, MaxEnt models provide a potentially powerful new tool to study functional connectivity in neuronal networks.

Prevalence of white matter pathways coming into a single white matter voxel orientation: The bottleneck issue in tractography.

Characterizing and understanding the limitations of diffusion MRI fiber tractography is a prerequisite for methodological advances and innovations which will allow these techniques to accurately map the connections of the human brain. The so‐called “crossing fiber problem” has received tremendous attention and has continuously triggered the community to develop novel approaches for disentangling distinctly oriented fiber populations. Perhaps an even greater challenge occurs when multiple white matter bundles converge within a single voxel, or throughout a single brain region, and share the same parallel orientation, before diverging and continuing towards their final cortical or sub‐cortical terminations. These so‐called “bottleneck” regions contribute to the ill‐posed nature of the tractography process, and lead to both false positive and false negative estimated connections. Yet, as opposed to the extent of crossing fibers, a thorough characterization of bottleneck regions has not been performed. The aim of this study is to quantify the prevalence of bottleneck regions. To do this, we use diffusion tractography to segment known white matter bundles of the brain, and assign each bundle to voxels they pass through and to specific orientations within those voxels (i.e. fixels). We demonstrate that bottlenecks occur in greater than 50‐70% of fixels in the white matter of the human brain. We find that all projection, association, and commissural fibers contribute to, and are affected by, this phenomenon, and show that even regions traditionally considered “single fiber voxels” often contain multiple fiber populations. Together, this study shows that a majority of white matter presents bottlenecks for tractography which may lead to incorrect or erroneous estimates of brain connectivity or quantitative tractography (i.e., tractometry), and underscores the need for a paradigm shift in the process of tractography and bundle segmentation for studying the fiber pathways of the human brain.

Numerical uncertainty in analytical pipelines lead to impactful variability in brain networks

The analysis of brain-imaging data requires complex processing pipelines to support findings on brain function or pathologies. Recent work has shown that variability in analytical decisions, small amounts of noise, or computational environments can lead to substantial differences in the results, endangering the trust in conclusions. We explored the instability of results by instrumenting a structural connectome estimation pipeline with Monte Carlo Arithmetic to introduce random noise throughout. We evaluated the reliability of the connectomes, the robustness of their features, and the eventual impact on analysis. The stability of results was found to range from perfectly stable (i.e. all digits of data significant) to highly unstable (i.e. 0 - 1 significant digits). This paper highlights the potential of leveraging induced variance in estimates of brain connectivity to reduce the bias in networks without compromising reliability, alongside increasing the robustness and potential upper-bound of their applications in the classification of individual differences. We demonstrate that stability evaluations are necessary for understanding error inherent to brain imaging experiments, and how numerical analysis can be applied to typical analytical workflows both in brain imaging and other domains of computational sciences, as the techniques used were data and context agnostic and globally relevant. Overall, while the extreme variability in results due to analytical instabilities could severely hamper our understanding of brain organization, it also affords us the opportunity to increase the robustness of findings.

Brain functional and effective connectivity based on electroencephalography recordings: A review.

Functional connectivity and effective connectivity of the human brain, representing statistical dependence and directed information flow between cortical regions, significantly contribute to the study of the intrinsic brain network and its functional mechanism. Many recent studies on electroencephalography (EEG) have been focusing on modeling and estimating brain connectivity due to increasing evidence that it can help better understand various brain neurological conditions. However, there is a lack of a comprehensive updated review on studies of EEG‐based brain connectivity, particularly on visualization options and associated machine learning applications, aiming to translate those techniques into useful clinical tools. This article reviews EEG‐based functional and effective connectivity studies undertaken over the last few years, in terms of estimation, visualization, and applications associated with machine learning classifiers. Methods are explored and discussed from various dimensions, such as either linear or nonlinear, parametric or nonparametric, time‐based, and frequency‐based or time‐frequency‐based. Then it is followed by a novel review of brain connectivity visualization methods, grouped by Heat Map, data statistics, and Head Map, aiming to explore the variation of connectivity across different brain regions. Finally, the current challenges of related research and a roadmap for future related research are presented.

Concurrent brain parcellation and connectivity estimation via co-clustering of resting state fMRI data: A novel approach.

Connectional topography mapping has been gaining widespread attention in human brain imaging studies. However, existing methods might not effectively utilize the information from neuroimaging data, thus hindering the understanding of the underlying connectional organization in the brain and uncovering the optimal clustering number from the data. In this study, we propose a novel method for the automated construction of inherent functional connectivity topography in a data‐driven manner by leveraging the power of co‐clustering‐based on resting state fMRI (rs‐fMRI) data. We propose the co‐clustering‐based method not only for concurrently parcellating two interconnected brain regions of interest (ROIs) under consideration into functionally homogenous subregions, but also for estimating the connectivity between these subregions from the two brain ROIs. In particular, we first model the connectional topography mapping as a co‐clustering‐based bipartite graph partitioning problem for constructing the inherent functional connectivity topography between the two interconnected brain ROIs. We also adopt an objective criterion, that is, silhouette width index measuring clustering quality, for determining the optimal number of clusters. The proposed method has been validated for mapping thalamocortical connectional topography based on rs‐fMRI data of 57 subjects. Validation results have demonstrated that our method identified the optimal solution with five pairs of mutually connected subregions of the thalamocortical system from the rs‐fMRI data, and could yield more meaningful, interpretable, and homogenous connectional topography than existing methods. The proposed method was further validated by the high symmetry of the mapped connectional topography between two hemispheres.

Brain network dysfunction associated with blood neurofilament light chain in autosomal dominant Alzheimer disease

AbstractBackgroundAlzheimer disease is characterized by accrual of amyloid‐b and tau, cortical thinning, and disruptions in brain connectivity. Recent reports suggest neurofilament light chain (NfL), a measure of brain damage and atrophy, is measurable in the blood and is predictive of presymptomatic cognitive decline in individuals with autosomal dominant Alzheimer Disease. We sought to investigate the relationship between serum blood estimates of NfL and functional brain connectivity. We hypothesized that increasing NfL levels would be associated with increasing disruption of within and between network connectivity.MethodWe performed neuroimaging and blood serum NfL assessments in a longitudinal sample of 78 mutation non‐carriers (NC) and 112 mutation carriers (MC) age 20‐65 enrolled in the Dominantly Inherited Alzheimer Network. Serum blood samples were collected and assayed in duplicate for NfL. Resting state‐functional MRI (rs‐fMRI) data were acquired on 3T Siemens scanners. For each subject, five minutes of low‐motion rs‐fMRI data were included (scrubbing with FD <0.2 mm). Functional connectivity (FC) was estimated using zero‐lag Pearson correlations calculated between 246 regions of interest (Figure 1A). NfL values were compared between mutation carriers and non‐carriers using non‐parametric Mann‐Whitney U tests (Figure 1B). We examined associations between FC and NfL using a Network Level Analysis (NLA) approach. Briefly, NLA uses non‐parametric test statistics and permutation testing to determine FC networks associated with NfL scores (Figure 1A).ResultNfL was correlated with a wide‐range of within and between‐network connectivity in MC but not NC subjects (Figure 2A). The five strongest associations with NfL were within the DMN, cingulo opercular (CO) and dorsal attention (DAN) networks. Specifically, greater levels of NfL were associated with reduced magnitude of within‐ and between‐network connectivity (Figure 2D&E).ConclusionOnly in the MC group was NfL correlated with deterioration of the DMN and reduced connectivity between the DMN and other brain systems. Reduced connectivity between DMN and CO and DAN with increasing atrophy may be associated with executive and cognitive decline following full progression to Alzheimer’s disease. The present study suggests that indirect measurement of cell death and brain atrophy with serum NfL corresponds to reduced functional connectivity in presymptomatic Alzheimer’s disease.

Non-negative data-driven mapping of structural connections with application to the neonatal brain

Mapping connections in the neonatal brain can provide insight into the crucial early stages of neurodevelopment that shape brain organisation and lay the foundations for cognition and behaviour. Diffusion MRI and tractography provide unique opportunities for such explorations, through estimation of white matter bundles and brain connectivity. Atlas-based tractography protocols, i.e. a priori defined sets of masks and logical operations in a template space, have been commonly used in the adult brain to drive such explorations. However, rapid growth and maturation of the brain during early development make it challenging to ensure correspondence and validity of such atlas-based tractography approaches in the developing brain. An alternative can be provided by data-driven methods, which do not depend on predefined regions of interest. Here, we develop a novel data-driven framework to extract white matter bundles and their associated grey matter networks from neonatal tractography data, based on non-negative matrix factorisation that is inherently suited to the non-negative nature of structural connectivity data. We also develop a non-negative dual regression framework to map group-level components to individual subjects. Using in-silico simulations, we evaluate the accuracy of our approach in extracting connectivity components and compare with an alternative data-driven method, independent component analysis. We apply non-negative matrix factorisation to whole-brain connectivity obtained from publicly available datasets from the Developing Human Connectome Project, yielding grey matter components and their corresponding white matter bundles. We assess the validity and interpretability of these components against traditional tractography results and grey matter networks obtained from resting-state fMRI in the same subjects. We subsequently use them to generate a parcellation of the neonatal cortex using data from 323 new-born babies and we assess the robustness and reproducibility of this connectivity-driven parcellation.

Statistical Analysis of Brain Connectivity Estimators during Distracted Driving.

This paper presents comparison of brain connectivity estimators of distracted drivers and non-distracted drivers based on statistical analysis. Twelve healthy volunteers with more than one year of driving experience participated in this experiment. Lane-keeping tasks and the Math problem-solving task were introduced in the experiment and EEGs (electroencephalogram) were used to record the brain waves. Granger-Geweke causality (GGC), directed transfer function (DTF) and partial directed coherence (PDC) brain connectivity estimation methods were used in brain connectivity analysis. Correlation test and a student's t-test were conducted on the connectivity matrixes. Results show a significant difference between the mean of distracted drivers and non-distracted driver's brain connectivity matrixes. GGC and DTF methods student's t-tests shows a p-value below 0.05 with the correlation coefficients varying from 0.62 to 0.38. PDC connectivity estimation method does not show a significant difference between the connectivity matrixes means unless it is compared with lane keeping task and the normal driving task. Furthermore, it shows a strong positive correlation between the connectivity matrixes.

On the two-step estimation of the cross-power spectrum for dynamical linear inverse problems

We consider the problem of reconstructing the cross-power spectrum of an unobservable multivariate stochastic process from indirect measurements of a second multivariate stochastic process, related to the first one through a linear operator. In the two-step approach, one would first compute a regularized reconstruction of the unobservable signal, and then compute an estimate of its cross-power spectrum from the regularized solution. We investigate whether the optimal regularization parameter for reconstruction of the signal also gives the best estimate of the cross-power spectrum. We show that the answer depends on the regularization method, and specifically we prove that, under a white Gaussian assumption: (i) when regularizing with truncated SVD the optimal parameter is the same; (ii) when regularizing with the Tikhonov method, the optimal parameter for the cross-power spectrum is lower than half the optimal parameter for the signal. We also provide evidence that a one-step approach would likely have better mathematical properties than the two-step approach. Our results apply particularly to the brain connectivity estimation from magneto/electro-encephalographic recordings and provide a formal interpretation of recent empirical results.

Novel Regional Activity Representation With Constrained Canonical Correlation Analysis for Brain Connectivity Network Estimation.

Inferring brain connectivity networks from fMRI data can take place at the Region of Interest (ROI) or voxel level. With most ROI-based approaches, the signals from same-ROI voxels are simply averaged, neglecting any inhomogeneity in each ROI and assuming that the same voxels will interact with different ROIs in a similar manner. In this paper, we propose a novel method of representing ROI activity and estimating brain connectivity that takes into account the regionally-specific nature of brain activity, the spatial location of concentrated activity, and activity in other ROIs. The proposed method is able to integrate intrinsic regional structures into a network modelling framework, which we call local activity constrained canonical correlation analysis (LA-cCCA). We evaluated LA-cCCA on both simulated and real fMRI data. The simulation results demonstrated that LA-cCCA had improved accuracy of the estimated brain connectivity networks compared to the average-signal or Principal Component Analysis (PCA)-based correlation methods and the Canonical Correlation Analysis (CCA) method. We further examined the performance of LA-cCCA on real fMRI data set from the Human Connectome Project. LA-cCCA outperformed the other three approaches in terms of connectivity reproducibility. The proposed method explores the potentials of regional activity representation and is a reliable model for connectivity network estimation. It may serve as a promising tool for studying both the healthy and diseased brain.