Statistical causality in the EEG for the study of cognitive functions in healthy and pathological brains

Understanding brain functions requires not only information about the spatial localization of neural activity, but also about the dynamic functional links between the involved groups of neurons, which do not work in an isolated way, but rather interact together through ingoing and outgoing connections. The work carried on during the three years of PhD course returns a methodological framework for the estimation of the causal brain connectivity and its validation on simulated and real datasets (EEG and pseudo-EEG) at scalp and source level. Important open issues like the selection of the best algorithms for the source reconstruction and for time-varying estimates were addressed. Moreover, after the application of such approaches on real datasets recorded from healthy subjects and post-stroke patients, we extracted neurophysiological indices describing in a stable and reliable way the properties of the brain circuits underlying different cognitive states in humans (attention, memory). More in detail: I defined and implemented a toolbox (SEED-G toolbox) able to provide a useful validation instrument addressed to researchers who conduct their activity in the field of brain connectivity estimation. It may have strong implication, especially in methodological advancements. It allows to test the ability of different estimators in increasingly less ideal conditions: low number of available samples and trials, high inter-trial variability (very realistic situations when patients are involved in protocols) or, again, time varying connectivity patterns to be estimate (where stationary hypothesis in wide sense failed). A first simulation study demonstrated the robustness and the accuracy of the PDC with respect to the inter-trials variability under a large range of conditions usually encountered in practice. The simulations carried on the time-varying algorithms allowed to highlight the performance of the existing methodologies in different conditions of signals amount and number of available trials. Moreover, the adaptation of the Kalman based algorithm (GLKF) I implemented, with the introduction of the preliminary estimation of the initial conditions for the algorithm, lead to significantly better performance. Another simulation study allowed to identify a tool combining source localization approaches and brain connectivity estimation able to provide accurate and reliable estimates as less as possible affected to the presence of spurious links due to the head volume conduction. The developed and tested methodologies were successfully applied on three real datasets. The first one was recorded from a group of healthy subjects performing an attention task that allowed to describe the brain circuit at scalp and source level related with three important attention functions: alerting, orienting and executive control. The second EEG dataset come from a group of healthy subjects performing a memory task. Also in this case, the approaches under investigation allowed to identify synthetic connectivity-based descriptors able to characterize the three main memory phases (encoding, storage and retrieval). For the last analysis I recorded EEG data from a group of stroke patients performing the same memory task before and after one month of cognitive rehabilitation. The promising results of this preliminary study showed the possibility to follow the changes observed at behavioural level by means of the introduced neurophysiological indices

Quantifying the effect of demixing approaches on directed connectivity estimated between reconstructed EEG sources

Electrical activity recorded on the scalp using electroencephalography (EEG) results from the mixing of signals originating from different regions of the brain as well as from artifactual sources. In order to investigate the role of distinct brain areas in a given experiment, the signal recorded on the sensors is typically projected back into the brain (source reconstruction) using algorithms that address the so-called EEG inverse problem. Once the activity of sources located inside of the brain has been reconstructed, it is often desirable to study the statistical dependencies among them, in particular to quantify directional dynamical interactions between brain areas. Unfortunately, even when performing source reconstruction, the superposition of signals that is due to the propagation of activity from sources to sensors cannot be completely undone, resulting in potentially biased estimates of directional functional connectivity. Here we perform a set of simulations involving interacting sources to quantify source connectivity estimation performance as a function of the location of the sources, their distance to each other, the noise level, the source reconstruction algorithm, and the connectivity estimator. The generated source activity was projected onto the scalp and projected back to the cortical level using two source reconstruction algorithms, linearly constrained minimum variance beamforming and Exact' low-resolution tomography (eLORETA). In source space, directed connectivity was estimated using multi-variate Granger causality and time-reversed Granger causality, and compared with the imposed ground truth. Our results demonstrate that all considered factors significantly affect the connectivity estimation performance

A social and ecological assessment of tropical land uses at multiple scales: the Sustainable Amazon Network

Science has a critical role to play in guiding more sustainable development trajectories. Here, we present the Sustainable Amazon Network (Rede Amazonia Sustentavel, RAS): a multidisciplinary research initiative involving more than 30 partner organizations working to assess both social and ecological dimensions of land-use sustainability in eastern Brazilian Amazonia. The research approach adopted by RAS offers three advantages for addressing land-use sustainability problems: (i) the collection of synchronized and co-located ecological and socioeconomic data across broad gradients of past and present human use; (ii) a nested sampling design to aid comparison of ecological and socioeconomic conditions associated with different land uses across local, landscape and regional scales; and (iii) a strong engagement with a wide variety of actors and non-research institutions. Here, we elaborate on these key features, and identify the ways in which RAS can help in highlighting those problems in most urgent need of attention, and in guiding improvements in land-use sustainability in Amazonia and elsewhere in the tropics. We also discuss some of the practical lessons, limitations and realities faced during the development of the RAS initiative so far.Keywords: Social–ecological systems, Tropical forests, Land use, Interdisciplinary research, Sustainability, Trade-off

Different Topological Properties of EEG-Derived Networks Describe Working Memory Phases as Revealed by Graph Theoretical Analysis

Several non-invasive imaging methods have contributed to shed light on the brain mechanisms underlying working memory (WM). The aim of the present study was to depict the topology of the relevant EEG-derived brain networks associated to distinct operations of WM function elicited by the Sternberg Item Recognition Task (SIRT) such as encoding, storage, and retrieval in healthy, middle age (46 ± 5 years) adults. High density EEG recordings were performed in 17 participants whilst attending a visual SIRT. Neural correlates of WM were assessed by means of a combination of EEG signal processing methods (i.e., time-varying connectivity estimation and graph theory), in order to extract synthetic descriptors of the complex networks underlying the encoding, storage, and retrieval phases of WM construct. The group analysis revealed that the encoding phase exhibited a significantly higher small-world topology of EEG networks with respect to storage and retrieval in all EEG frequency oscillations, thus indicating that during the encoding of items the global network organization could “optimally” promote the information flow between WM sub-networks. We also found that the magnitude of such configuration could predict subject behavioral performance when memory load increases as indicated by the negative correlation between Reaction Time and the local efficiency values estimated during the encoding in the alpha band in both 4 and 6 digits conditions. At the local scale, the values of the degree index which measures the degree of in- and out- information flow between scalp areas were found to specifically distinguish the hubs within the relevant sub-networks associated to each of the three different WM phases, according to the different role of the sub-network of regions in the different WM phases. Our findings indicate that the use of EEG-derived connectivity measures and their related topological indices might offer a reliable and yet affordable approach to monitor WM components and thus theoretically support the clinical assessment of cognitive functions in presence of WM decline/impairment, as it occurs after stroke

Estimating brain connectivity when few data points are available: Perspectives and limitations

Methods based on the use of multivariate autoregressive modeling (MVAR) have proved to be an accurate and flexible tool for the estimation of brain functional connectivity. The multivariate approach, however, implies the use of a model whose complexity (in terms of number of parameters) increases quadratically with the number of signals included in the problem. This can often lead to an underdetermined problem and to the condition of multicollinearity. The aim of this paper is to introduce and test an approach based on Ridge Regression combined with a modified version of the statistics usually adopted for these methods, to broaden the estimation of brain connectivity to those conditions in which current methods fail, due to the lack of enough data points. We tested the performances of this new approach, in comparison with the classical approach based on ordinary least squares (OLS), by means of a simulation study implementing different ground-truth networks, under different network sizes and different levels of data points. Simulation results showed that the new approach provides better performances, in terms of accuracy of the parameters estimation and false positives/false negatives rates, in all conditions related to a low data points/model dimension ratio, and may thus be exploited to estimate and validate estimated patterns at single-trial level or when short time data segments are available

Different Topological Properties of EEG-Derived Networks Describe Working Memory Phases as Revealed by Graph Theoretical Analysis

Several non-invasive imaging methods have contributed to shed light on the brain mechanisms underlying working memory (WM). The aim of the present study was to depict the topology of the relevant EEG-derived brain networks associated to distinct operations of WM function elicited by the Sternberg Item Recognition Task (SIRT) such as encoding, storage, and retrieval in healthy, middle age (46 ± 5 years) adults. High density EEG recordings were performed in 17 participants whilst attending a visual SIRT. Neural correlates of WM were assessed by means of a combination of EEG signal processing methods (i.e., time-varying connectivity estimation and graph theory), in order to extract synthetic descriptors of the complex networks underlying the encoding, storage, and retrieval phases of WM construct. The group analysis revealed that the encoding phase exhibited a significantly higher small-world topology of EEG networks with respect to storage and retrieval in all EEG frequency oscillations, thus indicating that during the encoding of items the global network organization could “optimally” promote the information flow between WM sub-networks. We also found that the magnitude of such configuration could predict subject behavioral performance when memory load increases as indicated by the negative correlation between Reaction Time and the local efficiency values estimated during the encoding in the alpha band in both 4 and 6 digits conditions. At the local scale, the values of the degree index which measures the degree of in- and out- information flow between scalp areas were found to specifically distinguish the hubs within the relevant sub-networks associated to each of the three different WM phases, according to the different role of the sub-network of regions in the different WM phases. Our findings indicate that the use of EEG-derived connectivity measures and their related topological indices might offer a reliable and yet affordable approach to monitor WM components and thus theoretically support the clinical assessment of cognitive functions in presence of WM decline/impairment, as it occurs after stroke. © 2018 Toppi, Astolfi, Risetti, Anzolin, Kober, Wood and Mattia

Investigating statistical differences in connectivity patterns properties at single subject level: A new resampling approach

Methods based on the multivariate autoregressive (MVAR) approach are commonly used for effective connectivity estimation as they allow to include all available sources into a unique model. To ensure high levels of accuracy for high model dimensions, all the observations are used to provide a unique estimation of the model, and thus of the network and its properties. The unavailability of a distribution of connectivity values for a single experimental condition prevents to perform statistical comparisons between different conditions at a single subject level. This is a major limitation, especially when dealing with the heterogeneity of clinical conditions presented by patients. In the present paper we proposed a novel approach to the construction of a distribution of connectivity in a single subject case. The proposed approach is based on small perturbations of the networks properties and allows to assess significant changes in brain connectivity indexes derived from graph theory. Its feasibility and applicability were investigated by means of a simulation study and an application to real EEG data