A framework for quantifying the coupling between brain connectivity and heartbeat dynamics: Insights into the disrupted network physiology in Parkinson's disease.

Parkinson's disease (PD) often shows disrupted brain connectivity and autonomic dysfunctions, progressing alongside with motor and cognitive decline. Recently, PD has been linked to a reduced sensitivity to cardiac inputs, that is, cardiac interoception. Altogether, those signs suggest that PD causes an altered brain-heart connection whose mechanisms remain unclear. Our study aimed to explore the large-scale network disruptions and the neurophysiology of disrupted interoceptive mechanisms in PD. We focused on examining the alterations in brain-heart coupling in PD and their potential connection to motor symptoms. We developed a proof-of-concept method to quantify relationships between the co-fluctuations of brain connectivity and cardiac sympathetic and parasympathetic activities. We quantified the brain-heart couplings from electroencephalogram and electrocardiogram recordings from PD patients on and off dopaminergic medication, as well as in healthy individuals at rest. Our results show that the couplings of fluctuating alpha and gamma connectivity with cardiac sympathetic dynamics are reduced in PD patients, as compared to healthy individuals. Furthermore, we show that PD patients under dopamine medication recover part of the brain-heart coupling, in proportion with the reduced motor symptoms. Our proposal offers a promising approach to unveil the physiopathology of PD and promoting the development of new evaluation methods for the early stages of the disease.

Exploration-Exploitation Paradigm for Networked Biological Systems.

The stochastic exploration of the configuration space and the exploitation of functional states underlie many biological processes. The evolutionary dynamics stands out as a remarkable example. Here, we introduce a novel formalism that mimics evolution and encodes a general exploration-exploitation dynamics for biological networks. We apply it to the brain wiring problem, focusing on the maturation of that of the nematode Caenorhabditis elegans. We demonstrate that a parsimonious maxent description of the adult brain combined with our framework is able to track down the entire developmental trajectory.

Measuring neuronal avalanches to inform brain-computer interfaces.

Large-scale interactions among multiple brain regions manifest as bursts of activations called neuronal avalanches, which reconfigure according to the task at hand and, hence, might constitute natural candidates to design brain-computer interfaces (BCIs). To test this hypothesis, we used source-reconstructed magneto/electroencephalography during resting state and a motor imagery task performed within a BCI protocol. To track the probability that an avalanche would spread across any two regions, we built an avalanche transition matrix (ATM) and demonstrated that the edges whose transition probabilities significantly differed between conditions hinged selectively on premotor regions in all subjects. Furthermore, we showed that the topology of the ATMs allows task-decoding above the current gold standard. Hence, our results suggest that neuronal avalanches might capture interpretable differences between tasks that can be used to inform brain-computer interfaces.

Statistical models of complex brain networks: a maximum entropy approach.

The brain is a highly complex system. Most of such complexity stems from the intermingled connections between its parts, which give rise to rich dynamics and to the emergence of high-level cognitive functions. Disentangling the underlying network structure is crucial to understand the brain functioning under both healthy and pathological conditions. Yet, analyzing brain networks is challenging, in part because their structure represents only one possible realization of a generative stochastic process which is in general unknown. Having a formal way to cope with such intrinsic variability is therefore central for the characterization of brain network properties. Addressing this issue entails the development of appropriate tools mostly adapted from network science and statistics. Here, we focus on a particular class of maximum entropy models for networks, i.e. exponential random graph models, as a parsimonious approach to identify the local connection mechanisms behind observed global network structure. Efforts are reviewed on the quest for basic organizational properties of human brain networks, as well as on the identification of predictive biomarkers of neurological diseases such as stroke. We conclude with a discussion on how emerging results and tools from statistical graph modeling, associated with forthcoming improvements in experimental data acquisition, could lead to a finer probabilistic description of complex systems in network neuroscience.

Vizaj-A free online interactive software for visualizing spatial networks.

In many fields of science and technology we are confronted with complex networks. Making sense of these networks often require the ability to visualize and explore their intermingled structure consisting of nodes and links. To facilitate the identification of significant connectivity patterns, many methods have been developed based on the rearrangement of the nodes so as to avoid link criss-cross. However, real networks are often embedded in a geometrical space and the nodes code for an intrinsic physical feature of the system that one might want to preserve. For these spatial networks, it is therefore crucial to find alternative strategies operating on the links and not on the nodes. Here, we introduce Vizaj a javascript web application to render spatial networks based on optimized geometrical criteria that reshape the link profiles. While optimized for 3D networks, Vizaj can also be used for 2D networks and offers the possibility to interactively customize the visualization via several controlling parameters, including network filtering and the effect of internode distance on the link trajectories. Vizaj is further equipped with additional options allowing to improve the final aesthetics, such as the color/size of both nodes and links, zooming/rotating/translating, and superimposing external objects. Vizaj is an open-source software which can be freely downloaded and updated via a github repository. Here, we provide a detailed description of its main features and algorithms together with a guide on how to use it. Finally, we validate its potential on several synthetic and real spatial networks from infrastructural to biological systems. We hope that Vizaj will help scientists and practitioners to make sense of complex networks and provide aesthetic while informative visualizations.

The impact of aging on human brain network target controllability.

Understanding how few distributed areas can steer large-scale brain activity is a fundamental question that has practical implications, which range from inducing specific patterns of behavior to counteracting disease. Recent endeavors based on network controllability provided fresh insights into the potential ability of single regions to influence whole brain dynamics through the underlying structural connectome. However, controlling the entire brain activity is often unfeasible and might not always be necessary. The question whether single areas can control specific target subsystems remains crucial, albeit still poorly explored. Furthermore, the structure of the brain network exhibits progressive changes across the lifespan, but little is known about the possible consequences in the controllability properties. To address these questions, we adopted a novel target controllability approach that quantifies the centrality of brain nodes in controlling specific target anatomo-functional systems. We then studied such target control centrality in human connectomes obtained from healthy individuals aged from 5 to 85. Main results showed that the sensorimotor system has a high influencing capacity, but it is difficult for other areas to influence it. Furthermore, we reported that target control centrality varies with age and that temporal-parietal regions, whose cortical thinning is crucial in dementia-related diseases, exhibit lower values in older people. By simulating targeted attacks, such as those occurring in focal stroke, we showed that the ipsilesional hemisphere is the most affected one regardless of the damaged area. Notably, such degradation in target control centrality was more evident in younger people, thus supporting early-vulnerability hypotheses after stroke.

Decreased brain network global efficiency after attachment memories retrieval in individuals with unresolved/disorganized attachment-related state of mind.

The main aim of the study was to examine how brain network metrics change after retrieval of attachment memories in individuals with unresolved/disorganized (U/D) attachment-related state of mind and those with organized/resolved (O/R) state of mind. We focused on three main network metrics associated with integration and segregation: global (Eglob) efficiency for the first function, local (Eloc) efficiency and modularity for the second. We also examined assortativity and centrality metrics. Electroencephalography (EEG) recordings were performed before and after the Adult Attachment Interview (AAI) in a sample of 50 individuals previously assessed for parenting quality. Functional connectivity matrices were constructed by means of the exact Low-Resolution Electromagnetic Tomography (eLORETA) software and then imported into MATLAB to compute brain network metrics. Compared to individuals with O/R attachment-related state of mind, those with U/D show a significant decrease in beta Eglob after AAI. No statistically significant difference among groups emerged in Eloc and modularity metrics after AAI, neither in assortativity nor in betweenness centrality. These results may help to better understand the neurophysiological patterns underlying the disintegrative effects of retrieving traumatic attachment memories in individuals with disorganized state of mind in relation to attachment.

Temporal exponential random graph models of longitudinal brain networks after stroke.

Plasticity after stroke is a complex phenomenon. Functional reorganization occurs not only in the perilesional tissue but throughout the brain. However, the local connection mechanisms generating such global network changes remain largely unknown. To address this question, time must be considered as a formal variable of the problem rather than a simple repeated observation. Here, we hypothesized that the presence of temporal connection motifs, such as the formation of temporal triangles (T) and edges (E) over time, would explain large-scale brain reorganization after stroke. To test our hypothesis, we adopted a statistical framework based on temporal exponential random graph models (tERGMs), where the aforementioned temporal motifs were implemented as parameters and adapted to capture global network changes after stroke. We first validated the performance on synthetic time-varying networks as compared to standard static approaches. Then, using real functional brain networks, we showed that estimates of tERGM parameters were sufficient to reproduce brain network changes from 2 weeks to 1 year after stroke. These temporal connection signatures, reflecting within-hemisphere segregation (T) and between hemisphere integration (E), were associated with patients' future behaviour. In particular, interhemispheric temporal edges significantly correlated with the chronic language and visual outcome in subcortical and cortical stroke, respectively. Our results indicate the importance of time-varying connection properties when modelling dynamic complex systems and provide fresh insights into modelling of brain network mechanisms after stroke.

Stepwise target controllability identifies dysregulations of macrophage networks in multiple sclerosis.

Identifying the nodes able to drive the state of a network is crucial to understand, and eventually control, biological systems. Despite recent advances, such identification remains difficult because of the huge number of equivalent controllable configurations, even in relatively simple networks. Based on the evidence that in many applications it is essential to test the ability of individual nodes to control a specific target subset, we develop a fast and principled method to identify controllable driver-target configurations in sparse and directed networks. We demonstrate our approach on simulated networks and experimental gene networks to characterize macrophage dysregulation in human subjects with multiple sclerosis.

A machine learning approach to screen for preclinical Alzheimer's disease.

Combining multimodal biomarkers could help in the early diagnosis of Alzheimer's disease (AD). We included 304 cognitively normal individuals from the INSIGHT-preAD cohort. Amyloid and neurodegeneration were assessed on 18F-florbetapir and 18F-fluorodeoxyglucose PET, respectively. We used a nested cross-validation approach with non-invasive features (electroencephalography [EEG], APOE4 genotype, demographic, neuropsychological and MRI data) to predict: 1/ amyloid status; 2/ neurodegeneration status; 3/ decline to prodromal AD at 5-year follow-up. Importantly, EEG was most strongly predictive of neurodegeneration, even when reducing the number of channels from 224 down to 4, as 4-channel EEG best predicted neurodegeneration (negative predictive value [NPV] = 82%, positive predictive value [PPV] = 38%, 77% specificity, 45% sensitivity). The combination of demographic, neuropsychological data, APOE4 and hippocampal volumetry most strongly predicted amyloid (80% NPV, 41% PPV, 70% specificity, 58% sensitivity) and most strongly predicted decline to prodromal AD at 5 years (97% NPV, 14% PPV, 83% specificity, 50% sensitivity). Thus, machine learning can help to screen patients at high risk of preclinical AD using non-invasive and affordable biomarkers.

Phase/Amplitude Synchronization of Brain Signals During Motor Imagery BCI Tasks.

In the last decade, functional connectivity (FC) has been increasingly adopted based on its ability to capture statistical dependencies between multivariate brain signals. However, the role of FC in the context of brain-computer interface applications 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 we 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 we 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 in the sensorimotor areas, those based on imaginary-coherence were significantly 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 eventually assessed the potential of these network connectivity features in a simple off-line classification scenario. 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.

Network-based brain-computer interfaces: principles and applications.

Brain-computer interfaces (BCIs) make possible to interact with the external environment by decoding the mental intention of individuals. BCIs can therefore be used to address basic neuroscience questions but also to unlock a variety of applications from exoskeleton control to neurofeedback rehabilitation. In general, BCI usability depends on the ability to comprehensively characterize brain functioning and correctly identify the user's mental state. To this end, much of the efforts have focused on improving the classification algorithms taking into account localized brain activities as input features. Despite considerable improvement BCI performance is still unstable and, as a matter of fact, current features represent oversimplified descriptors of brain functioning. In the last decade, growing evidence has shown that the brain works as a networked system composed of multiple specialized and spatially distributed areas that dynamically integrate information. While more complex, looking at how remote brain regions functionally interact represents a grounded alternative to better describe brain functioning. Thanks to recent advances in network science, i.e. a modern field that draws on graph theory, statistical mechanics, data mining and inferential modeling, scientists have now powerful means to characterize complex brain networks derived from neuroimaging data. Notably, summary features can be extracted from brain networks to quantitatively measure specific organizational properties across a variety of topological scales. In this topical review, we aim to provide the state-of-the-art supporting the development of a network theoretic approach as a promising tool for understanding BCIs and improve usability.

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

OBJECTIVE: Motor imagery-based brain-computer interfaces (BCIs) use an individual's ability to volitionally modulate localized brain activity, often 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. Formal experiments designed to probe the nature of BCI learning have offered initial evidence that coherent activity across spatially distributed and functionally 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. APPROACH: 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 magnetoencephalography. 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. MAIN RESULTS: We find that learning is marked by diffuse brain-behavior relations: good learners displayed many subgraphs whose temporal expression tracked performance. 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 sensors near 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 sensors located near brain regions important for attention. SIGNIFICANCE: The nature of our contribution to the neuroscience of BCI learning is therefore both computational and theoretical; we first use a minimally-constrained, individual specific method of identifying mesoscale structure in dynamic brain activity to show how global connectivity and interactions between distributed networks supports BCI learning, and then we use a formal network model of control to lend theoretical support to the hypothesis that these identified subgraphs are well suited to modulate attention.

Functional disconnection of associative cortical areas predicts performance during BCI training.

Brain-computer interfaces (BCIs) have been largely developed to allow communication, control, and neurofeedback in human beings. Despite their great potential, BCIs perform inconsistently across individuals and the neural processes that enable humans to achieve good control remain poorly understood. To address this question, we performed simultaneous high-density electroencephalographic (EEG) and magnetoencephalographic (MEG) recordings in a motor imagery-based BCI training involving a group of healthy subjects. After reconstructing the signals at the cortical level, we showed that the reinforcement of motor-related activity during the BCI skill acquisition is paralleled by a progressive disconnection of associative areas which were not directly targeted during the experiments. Notably, these network connectivity changes reflected growing automaticity associated with BCI performance and predicted future learning rate. Altogether, our findings provide new insights into the large-scale cortical organizational mechanisms underlying BCI learning, which have implications for the improvement of this technology in a broad range of real-life applications.

EEG evidence of compensatory mechanisms in preclinical Alzheimer's disease.

Early biomarkers are needed to identify individuals at high risk of preclinical Alzheimer's disease and to better understand the pathophysiological processes of disease progression. Preclinical Alzheimer's disease EEG changes would be non-invasive and cheap screening tools and could also help to predict future progression to clinical Alzheimer's disease. However, the impact of amyloid-ß deposition and neurodegeneration on EEG biomarkers needs to be elucidated. We included participants from the INSIGHT-preAD cohort, which is an ongoing single-centre multimodal observational study that was designed to identify risk factors and markers of progression to clinical Alzheimer's disease in 318 cognitively normal individuals aged 70-85 years with a subjective memory complaint. We divided the subjects into four groups, according to their amyloid status (based on 18F-florbetapir PET) and neurodegeneration status (evidenced by 18F-fluorodeoxyglucose PET brain metabolism in Alzheimer's disease signature regions). The first group was amyloid-positive and neurodegeneration-positive, which corresponds to stage 2 of preclinical Alzheimer's disease. The second group was amyloid-positive and neurodegeneration-negative, which corresponds to stage 1 of preclinical Alzheimer's disease. The third group was amyloid-negative and neurodegeneration-positive, which corresponds to 'suspected non-Alzheimer's pathophysiology'. The last group was the control group, defined by amyloid-negative and neurodegeneration-negative subjects. We analysed 314 baseline 256-channel high-density eyes closed 1-min resting state EEG recordings. EEG biomarkers included spectral measures, algorithmic complexity and functional connectivity assessed with a novel information-theoretic measure, weighted symbolic mutual information. The most prominent effects of neurodegeneration on EEG metrics were localized in frontocentral regions with an increase in high frequency oscillations (higher beta and gamma power) and a decrease in low frequency oscillations (lower delta power), higher spectral entropy, higher complexity and increased functional connectivity measured by weighted symbolic mutual information in theta band. Neurodegeneration was associated with a widespread increase of median spectral frequency. We found a non-linear relationship between amyloid burden and EEG metrics in neurodegeneration-positive subjects, either following a U-shape curve for delta power or an inverted U-shape curve for the other metrics, meaning that EEG patterns are modulated differently depending on the degree of amyloid burden. This finding suggests initial compensatory mechanisms that are overwhelmed for the highest amyloid load. Together, these results indicate that EEG metrics are useful biomarkers for the preclinical stage of Alzheimer's disease.

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 because of 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-that is, the probability of a region to be in the multiplex core-significantly decreased in AD patients as result of a random disconnection 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.

Quality Assessment of Single-Channel EEG for Wearable Devices.

The recent embedding of electroencephalographic (EEG) electrodes in wearable devices raises the problem of the quality of the data recorded in such uncontrolled environments. These recordings are often obtained with dry single-channel EEG devices, and may be contaminated by many sources of noise which can compromise the detection and characterization of the brain state studied. In this paper, we propose a classification-based approach to effectively quantify artefact contamination in EEG segments, and discriminate muscular artefacts. The performance of our method were assessed on different databases containing either artificially contaminated or real artefacts recorded with different type of sensors, including wet and dry EEG electrodes. Furthermore, the quality of unlabelled databases was evaluated. For all the studied databases, the proposed method is able to rapidly assess the quality of the EEG signals with an accuracy higher than 90%. The obtained performance suggests that our approach provide an efficient, fast and automated quality assessment of EEG signals from low-cost wearable devices typically composed of a dry single EEG channel.

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.

Integrating EEG and MEG Signals to Improve Motor Imagery Classification in Brain-Computer Interface.

We adopted a fusion approach that combines features from simultaneously recorded electroencephalogram (EEG) and magnetoencephalogram (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 noninvasive BCIs.