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Fabrizio De Vico Fallani

Publications and source records attributed to Fabrizio De Vico Fallani.

36 records · Page 2Linked to original sources

Step-wise target controllability identifies dysregulated pathways of macrophage networks in multiple sclerosis

Identifying the nodes that have the potential to influence the state of a network is a relevant question for many complex systems. In many applications it is often essential to test the ability of an individual node to control a specific target subset of the network. In biological networks, this might provide precious information on how single genes regulate the expression of specific groups of molecules in the cell. Taking into account these constraints, we propose an optimized heuristic based on the Kalman rank condition to quantify the centrality of a node as the number of target nodes it can control. By introducing a hierarchy among the nodes in the target set, and performing a step-wise research, we ensure for sparse and directed networks the identification of a controllable driver-target configuration in a significantly reduced space and time complexity. We show how the method works for simple network configurations, then we use it to characterize the inflammatory pathways in molecular gene networks associated with macrophage dysfunction in patients with multiple sclerosis. Results indicate that the targeted secreted molecules can in general be controlled by a large number of driver nodes (51%) involved in different cell functions, i.e. sensing, signaling and transcription. However, during the inflammatory response only a moderate fraction of all the possible driver-target pairs are significantly coactivated, as measured by gene expression data obtained from human blood samples. Notably, they differ between multiple sclerosis patients and healthy controls, and we find that this is related to the presence of dysregulated genes along the controllable walks. Our method, that we name step-wise target controllability, represents a practical solution to identify controllable driver-target configurations in directed complex networks and test their relevance from a functional perspective.

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Phase/amplitude synchronization of brain signals during motor imagery BCI tasks

The extraction of brain functioning features is a crucial step in the definition of brain-computer interfaces (BCIs). In the last decade, functional connectivity (FC) estimators have been increasingly explored based on their ability to capture synchronization between multivariate brain signals. However, the underlying neurophysiological mechanisms and the extent to which they can improve performance in BCI-related tasks, is still poorly understood. To address this gap in knowledge, we considered a group of 20 healthy subjects during an EEG-based hand motor imagery (MI) task. We studied two well-established FC estimators, i.e. spectral- and imaginary-coherence, and investigated how they were modulated by the MI task. We characterized the resulting FC networks by extracting the strength of connectivity of each EEG sensor and compared the discriminant power with respect to standard power spectrum features. At the group level, results showed that while spectral-coherence based network features were increasing the controlateral motor area, those based on imaginary-coherence were decreasing. We demonstrated that this opposite, but complementary, behavior was respectively determined by the increase in amplitude and phase synchronization between the brain signals. At the individual level, we proved that including these network connectivity features in the classification of MI mental states led to an overall improvement in accuracy. Taken together, our results provide fresh insights into the oscillatory mechanisms subserving brain network changes during MI and offer new perspectives to improve BCI performance.

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Learning in brain-computer interface control evidenced by joint decomposition of brain and behavior

Motor imagery-based brain-computer interfaces (BCIs) use an individuals ability to volitionally modulate localized brain activity as a therapy for motor dysfunction or to probe causal relations between brain activity and behavior. However, many individuals cannot learn to successfully modulate their brain activity, greatly limiting the efficacy of BCI for therapy and for basic scientific inquiry. Previous research suggests that coherent activity across diverse cognitive systems is a hallmark of individuals who can successfully learn to control the BCI. However, little is known about how these distributed networks interact through time to support learning. Here, we address this gap in knowledge by constructing and applying a multimodal network approach to decipher brain-behavior relations in motor imagery-based brain-computer interface learning using MEG. Specifically, we employ a minimally constrained matrix decomposition method (non-negative matrix factorization) to simultaneously identify regularized, covarying subgraphs of functional connectivity, to assess their similarity to task performance, and to detect their time-varying expression. Individuals also displayed marked variation in the spatial properties of subgraphs such as the connectivity between the frontal lobe and the rest of the brain, and in the temporal properties of subgraphs such as the stage of learning at which they reached maximum expression. From these observations, we posit a conceptual model in which certain subgraphs support learning by modulating brain activity in regions important for sustaining attention. To test this model, we use tools that stipulate regional dynamics on a networked system (network control theory), and find that good learners display a single subgraph whose temporal expression tracked performance and whose architecture supports easy modulation of brain regions important for attention.

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Temporal connection signatures of human brain networks after stroke

Plasticity after stroke is a complex phenomenon initiated by the functional reorganization of the brain, especially in the perilesional tissue. At macroscales, the reestablishment of segregation within the affected hemisphere and interhemispheric integration has been extensively documented in the reconfiguration of brain networks. However, the local connection mechanisms generating such global network changes are still largely unknown as well as their potential to better predict the outcome of patients. To address this question, time must be considered as a formal variable of the problem and not just a simple repeated observation. Here, we hypothesize that the temporal formation of basic connection blocks such as intermodule edges and intramodule triangles would be sufficient to determine the large-scale brain reorganization after stroke. To test our hypothesis, we adopted a statistical approach based on temporal exponential random graph models (tERGMs). First, we validated the overall performance on synthetic time-varying networks simulating the reconfiguration process after stroke. Then, using longitudinal functional connectivity measurements of resting-state brain activity, we showed that both the formation of triangles within the affected hemisphere and interhemispheric links are sufficient to reproduce the longitudinal brain network changes from 2 weeks to 1 year after the stroke. Finally, we showed that these temporal connection mechanisms are over-expressed in the subacute phase as compared to healthy controls and predicted the chronic language and visual outcome respectively in patients with subcortical and cortical lesions, whereas static approaches failed to do so. Our results indicate the importance of considering time-varying connection properties when modeling dynamic complex systems and provide fresh insights into the network mechanisms of stroke recovery.

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Disrupted core-periphery structure of multimodal brain networks in Alzheimer's Disease

In Alzheimer's disease (AD), the progressive atrophy leads to aberrant network reconfigurations both at structural and functional levels. In such network reorganization, the core and peripheral nodes appear to be crucial for the prediction of clinical outcome due to their ability to influence large-scale functional integration. However, the role of the different types of brain connectivity in such prediction still remains unclear. Using a multiplex network approach we integrated information from DWI, fMRI and MEG brain connectivity to extract an enriched description of the core-periphery structure in a group of AD patients and age-matched controls. Globally, the regional coreness - i.e., the probability of a region to be in the multiplex core - significantly decreased in AD patients as a result of the randomization process initiated by the neurodegeneration. Locally, the most impacted areas were in the core of the network - including temporal, parietal and occipital areas - while we reported compensatory increments for the peripheral regions in the sensorimotor system. Furthermore, these network changes significantly predicted the cognitive and memory impairment of patients. Taken together these results indicate that a more accurate description of neurodegenerative diseases can be obtained from the multimodal integration of neuroimaging-derived network data.

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Network neuroscience for optimizing brain-computer interfaces

Human-machine interactions are being increasingly explored to create alternative ways of communication and to improve our daily life. Based on a classification of the user's intention from the user's underlying neural activity, brain-computer interfaces (BCIs) allow direct interactions with the external environment while bypassing the traditional effector of the musculoskeletal system. Despite the enormous potential of BCIs, there are still a number of challenges that limit their societal impact, ranging from the correct decoding of a human's thoughts, to the application of effective learning strategies. Despite several important engineering advances, the basic neuroscience behind these challenges remains poorly explored. Indeed, BCIs involve complex dynamic changes related to neural plasticity at a diverse range of spatiotemporal scales. One promising antidote to this complexity lies in network science, which provides a natural language in which to model the organizational principles of brain architecture and function as manifest in its interconnectivity. Here, we briefly review the main limitations currently affecting BCIs, and we offer our perspective on how they can be addressed by means of network theoretic approaches. We posit that the emerging field of network neuroscience will prove to be an effective tool to unlock human-machine interactions.

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Integrating EEG and MEG signals to improve motor imagery classification in brain-computer interfaces

We propose a fusion approach that combines features from simultaneously recorded electroencephalographic (EEG) and magnetoencephalographic (MEG) signals to improve classification performances in motor imagery-based brain-computer interfaces (BCIs). We applied our approach to a group of 15 healthy subjects and found a significant classification performance enhancement as compared to standard single-modality approaches in the alpha and beta bands. Taken together, our findings demonstrate the advantage of considering multimodal approaches as complementary tools for improving the impact of non-invasive BCIs.

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Surrogate-based artifact removal from single-channel EEG

The recent emergence and success of electroencephalography (EEG) in low-cost portable devices, has opened the door to a new generation of applications processing a small number of EEG channels for health monitoring and brain-computer interfacing. These recordings are, however, contaminated by many sources of noise degrading the signals of interest, thus compromising the interpretation of the underlying brain state. In this work, we propose a new data-driven algorithm to effectively remove ocular and muscular artifacts from single-channel EEG: the surrogate-based artifact removal (SuBAR). Methods: By means of the time-frequency analysis of surrogate data, our approach is able to identify and filter automatically ocular and muscular artifacts embedded in single-channel EEG. Results: In a comparative study using artificially contami- nated EEG signals, the efficacy of the algorithm in terms of noise removal and signal distortion was superior to other traditionally-employed single-channel EEG denoising techniques: wavelet thresholding and the canonical correlation analysis combined with an advanced version of the empirical mode decomposition. Even in the presence of mild and severe artifacts, our artifact removal method provides a relative error 4 to 5 times lower than traditional techniques. Significance: In view of these results, the SuBAR method is a promising solution for mobile environments, such as ambulatory healthcare systems, sleep stage scoring or anesthesia monitoring, where very few EEG channels or even a single channel is available.

physics.data-an↗

Multiplex core-periphery organization of the human connectome

The behavior of many complex systems is determined by a core of densely interconnected units. While many methods are available to identify the core of a network when connections between nodes are all of the same type, a principled approach to define the core when multiple types of connectivity are allowed is still lacking. Here we introduce a general framework to define and extract the core-periphery structure of multi-layer networks by explicitly taking into account the connectivity of the nodes at each layer. We show how our method works on synthetic networks with different size, density, and overlap between the cores at the different layers. We then apply the method to multiplex brain networks whose layers encode information both on the anatomical and the functional connectivity among regions of the human cortex. Results confirm the presence of the main known hubs, but also suggest the existence of novel brain core regions that have been discarded by previous analysis which focused exclusively on the structural layer. Our work is a step forward in the identification of the core of the human connectome, and contributes to shed light to a fundamental question in modern neuroscience.

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Loss of brain inter-frequency hubs in Alzheimer's disease

Alzheimer's disease (AD) causes alterations of brain network structure and function. The latter consists of connectivity changes between oscillatory processes at different frequency channels. We proposed a multi-layer network approach to analyze multiple-frequency brain networks inferred from magnetoencephalographic recordings during resting-states in AD subjects and age-matched controls. Main results showed that brain networks tend to facilitate information propagation across different frequencies, as measured by the multi-participation coefficient (MPC). However, regional connectivity in AD subjects was abnormally distributed across frequency bands as compared to controls, causing significant decreases of MPC. This effect was mainly localized in association areas and in the cingulate cortex, which acted, in the healthy group, as a true inter-frequency hub. MPC values significantly correlated with memory impairment of AD subjects, as measured by the total recall score. Most predictive regions belonged to components of the default-mode network that are typically affected by atrophy, metabolism disruption and amyloid-beta deposition. We evaluated the diagnostic power of the MPC and we showed that it led to increased classification accuracy (78.39%) and sensitivity (91.11%). These findings shed new light on the brain functional alterations underlying AD and provide analytical tools for identifying multi-frequency neural mechanisms of brain diseases.

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A statistical model for brain networks inferred from large-scale electrophysiological signals

Network science has been extensively developed to characterize structural properties of complex systems, including brain networks inferred from neuroimaging data. As a result of the inference process, networks estimated from experimentally obtained biological data, represent one instance of a larger number of realizations with similar intrinsic topology. A modeling approach is therefore needed to support statistical inference on the bottom-up local connectivity mechanisms influencing the formation of the estimated brain networks. We adopted a statistical model based on exponential random graphs (ERGM) to reproduce brain networks, or connectomes, estimated by spectral coherence between high-density electroencephalographic (EEG) signals. We validated this approach in a dataset of 108 healthy subjects during eyes-open (EO) and eyes-closed (EC) resting-state conditions. Results showed that the tendency to form triangles and stars, reflecting clustering and node centrality, better explained the global properties of the EEG connectomes as compared to other combinations of graph metrics. Synthetic networks generated by this model configuration replicated the characteristic differences found in brain networks, with EO eliciting significantly higher segregation in the alpha frequency band (8-13 Hz) as compared to EC. Furthermore, the fitted ERGM parameter values provided complementary information showing that clustering connections are significantly more represented from EC to EO in the alpha range, but also in the beta band (14-29 Hz), which is known to play a crucial role in cortical processing of visual input and externally oriented attention. These findings support the current view of the brain functional segregation and integration in terms of modules and hubs, and provide a statistical approach to extract new information on the (re)organizational mechanisms in healthy and diseased brains.

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A topological criterion for filtering information in complex brain networks

In many biological systems, the network of interactions between the elements can only be inferred from experimental measurements. In neuroscience, non-invasive imaging tools are extensively used to derive either structural or functional brain networks in-vivo. As a result of the inference process, we obtain a matrix of values corresponding to an unrealistic fully connected and weighted network. To turn this into a useful sparse network, thresholding is typically adopted to cancel a percentage of the weakest connections. The structural properties of the resulting network depend on how much of the inferred connectivity is eventually retained. However, how to fix this threshold is still an open issue. We introduce a criterion, the efficiency cost optimization (ECO), to select a threshold based on the optimization of the trade-off between the efficiency of a network and its wiring cost. We prove analytically and we confirm through numerical simulations that the connection density maximizing this trade-off emphasizes the intrinsic properties of a given network, while preserving its sparsity. Moreover, this density threshold can be determined a-priori, since the number of connections to filter only depends on the network size according to a power-law. We validate this result on several brain networks, from micro- to macro-scales, obtained with different imaging modalities. Finally, we test the potential of ECO in discriminating brain states with respect to alternative filtering methods. ECO advances our ability to analyze and compare biological networks, inferred from experimental data, in a fast and principled way.

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Hierarchy of neural organization in the embryonic spinal cord: Granger-causality graph analysis of in vivo calcium imaging data

The recent development of genetically encoded calcium indicators enables monitoring in vivo the activity of neuronal populations. Most analysis of these calcium transients relies on linear regression analysis based on the sensory stimulus applied or the behavior observed. To estimate the basic properties of the functional neural circuitry, we propose a network-based approach based on calcium imaging recorded at single cell resolution. Differently from previous analysis based on cross-correlation, we used Granger-causality estimates to infer activity propagation between the activities of different neurons. The resulting functional networks were then modeled as directed graphs and characterized in terms of connectivity and node centralities. We applied our approach to calcium transients recorded at low frequency (4 Hz) in ventral neurons of the zebrafish spinal cord at the embryonic stage when spontaneous coiling of the tail occurs. Our analysis on population calcium imaging data revealed a strong ipsilateral connectivity and a characteristic hierarchical organization of the network hubs that supported established propagation of activity from rostral to caudal spinal cord. Our method could be used for detecting functional defects in neuronal circuitry during development and pathological conditions.

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Graph analysis of functional brain networks: practical issues in translational neuroscience

The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires a know-how of all the methodological steps of the processing pipeline that manipulates the input brain signals and extract the functional network properties. On the other hand, a knowledge of the neural phenomenon under study is required to perform physiological-relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes.

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Human brain distinctiveness based on EEG spectral coherence connectivity

The use of EEG biometrics, for the purpose of automatic people recognition, has received increasing attention in the recent years. Most of current analysis rely on the extraction of features characterizing the activity of single brain regions, like power-spectrum estimates, thus neglecting possible temporal dependencies between the generated EEG signals. However, important physiological information can be extracted from the way different brain regions are functionally coupled. In this study, we propose a novel approach that fuses spectral coherencebased connectivity between different brain regions as a possibly viable biometric feature. The proposed approach is tested on a large dataset of subjects (N=108) during eyes-closed (EC) and eyes-open (EO) resting state conditions. The obtained recognition performances show that using brain connectivity leads to higher distinctiveness with respect to power-spectrum measurements, in both the experimental conditions. Notably, a 100% recognition accuracy is obtained in EC and EO when integrating functional connectivity between regions in the frontal lobe, while a lower 97.41% is obtained in EC (96.26% in EO) when fusing power spectrum information from centro-parietal regions. Taken together, these results suggest that functional connectivity patterns represent effective features for improving EEG-based biometric systems.

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Non-parametric resampling of random walks for spectral network clustering

Parametric resampling schemes have been recently introduced in complex network analysis with the aim of assessing the statistical significance of graph clustering and the robustness of community partitions. We propose here a method to replicate structural features of complex networks based on the non-parametric resampling of the transition matrix associated with an unbiased random walk on the graph. We test this bootstrapping technique on synthetic and real-world modular networks and we show that the ensemble of replicates obtained through resampling can be used to improve the performance of standard spectral algorithms for community detection.

physics.soc-ph↗

Multiscale Topological Properties Of Functional Brain Networks During Motor Imagery After Stroke

In recent years, network analyses have been used to evaluate brain reorganization following stroke. However, many studies have often focused on single topological scales, leading to an incomplete model of how focal brain lesions affect multiple network properties simultaneously and how changes on smaller scales influence those on larger scales. In an EEG-based experiment on the performance of hand motor imagery (MI) in 20 patients with unilateral stroke, we observed that the anatomic lesion affects the functional brain network on multiple levels. In the beta (13-30 Hz) frequency band, the MI of the affected hand (Ahand) elicited a significantly lower smallworldness and local efficiency (Eloc) versus the unaffected hand (Uhand). Notably, the abnormal reduction in Eloc significantly depended on the increase in interhemispheric connectivity, which was in turn determined primarily by the rise in regional connectivity in the parieto-occipital sites of the affected hemisphere. Further, in contrast to the Uhand MI, in which significantly high connectivity was observed for the contralateral sensorimotor regions of the unaffected hemisphere, the regions that increased in connection during the Ahand MI lay in the frontal and parietal regions of the contralaterally affected hemisphere. Finally, the overall sensorimotor function of our patients, as measured by Fugl-Meyer Assessment (FMA) index, was significantly predicted by the connectivity of their affected hemisphere. These results increase our understanding of stroke-induced alterations in functional brain networks.

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Cluster structure of functional networks estimated from high-resolution EEG data

We study the topological properties of functional connectivity patterns among cortical areas in the frequency domain. The cortical networks were estimated from high-resolution EEG recordings in a group of spinal cord injured patients and in a group of healthy subjects, during the preparation of a limb movement. We first evaluate global and local efficiency, as indicators of the structural connectivity respectively at a global and local scale. Then, we use the Markov Clustering method to analyse the division of the network into community structures. The results indicate large differences between the injured patients and the healthy subjects. In particular, the networks of spinal cord injured patient exhibited a higher density of efficient clusters. In the Alpha (7-12 Hz) frequency band, the two observed largest communities were mainly composed by the cingulate motor areas with the supplementary motor areas, and by the pre-motor areas with the right primary motor area of the foot. This functional separation strengthens the hypothesis of a compensative mechanism due to the partial alteration in the primary motor areas because of the effects of the spinal cord injury.

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