A novel approach to measure brain-to-brain spatial and temporal alignment during positive empathy.

Empathy is defined as the ability to vicariously experience others' suffering (vicarious pain) or feeling their joy (vicarious reward). While most neuroimaging studies have focused on vicarious pain and describe similar neural responses during the observed and the personal negative affective involvement, only initial evidence has been reported for the neural responses to others' rewards and positive empathy. Here, we propose a novel approach, based on the simultaneous recording of multi-subject EEG signals and exploiting the wavelet coherence decomposition to measure the temporal alignment between ERPs in a dyad of interacting subjects. We used the Third-Party Punishment (TPP) paradigm to elicit the personal and vicarious experiences. During a positive experience, we observed the simultaneous presence in both agents of the Late Positive Potential (LPP), an ERP component related to emotion processing, as well as the existence of an inter-subject ERPs synchronization in the related time window. Moreover, the amplitude of the LPP synchronization was modulated by the presence of a human-agent. Finally, the localized brain circuits subtending the ERP-synchronization correspond to key-regions of personal and vicarious reward. Our findings suggest that the temporal and spatial ERPs alignment might be a novel and direct proxy measure of empathy.

Low Frequency Brain Oscillations during the execution and imagination of simple hand movements for Brain-Computer Interface applications.

Low Frequency Brain Oscillations (LFOs) are brief periods of oscillatory activity in delta and lower theta band that appear at motor cortical areas before and around movement onset. It has been shown that LFO power decreases in post-stroke patients and re-emerges with motor functional recovery. To date, LFOs have not yet been explored during the motor execution (ME) and imagination (MI) of simple hand movements, often used in BCI-supported motor rehabilitation protocols post-stroke. This study aims at analyzing the LFOs during the ME and MI of the finger extension task in a sample of 10 healthy subjects and 2 stroke patients in subacute phase. The results showed that LFO power peaks occur in the preparatory phase of both ME and MI tasks on the sensorimotor channels in healthy subjects and their alterations in stroke patients. Clinical Relevance- Results suggest that LFOs could be explored as biomarker of the motor function recovery in rehabilitative protocols based on the movement imagination.

Cortico-Muscular Coupling Allows to Discriminate Different Types of Hand Movements.

Cortico-muscular coupling (CMC) could be used as potential input of a novel hybrid Brain-Computer Interface (hBCI) for motor re-learning after stroke. Here, we aim of addressing the design of a hBCI able to classify different movement tasks taking into account the interplay between the cerebral and residual or recovered muscular activity involved in a given movement. Hence, we compared the performances of four classification methods based on CMC features to evaluate their ability in discriminating finger extension from grasping movements executed by 17 healthy subjects. We also explored how the variation in the dimensionality of the feature domain would influence the different classifier performances. Results showed that, regardless of the model, few CMC features (up to 10) allow for a successful classification of two different movements type. Moreover, support vector machine classifier with linear kernel showed the best trade-off between performances and system usability (few electrodes). Thus, these results suggest that a hBCI based on brain-muscular interplay holds the potential to enable more informed neural plasticity and functional motor recovery after stroke. Furthermore, this CMC-based BCI could also allow for a more "natural control" (l.e., that resembling physiological control) of prosthetic devices.

Distinctive physiological muscle synergy patterns define the Box and Block Task execution as revealed by electromyographic features.

Stroke survivors experience muscular pattern alterations of the upper limb that decrease their ability to perform daily-living activities. The Box and Block test (BBT) is widely used to assess the unilateral manual dexterity. Although BBT provides insights into functional performance, it returns limited information about the mechanisms contributing to the impaired movement. This study aims at exploring the BBT by means of muscle synergies analysis during the execution of BBT in a sample of 12 healthy participants with their dominant and non-dominant upper limb. Results revealed that: (i) the BBT can be described by 1 or 2 synergies; the number of synergies (ii) does not differ between dominant and non-dominant sides and (iii) varies considering each phase of the task; (iv) the transfer phase requires more synergies. Clinical Relevance- This preliminary study characterizes muscular synergies during the BBT task in order to establish normative patterns that could assist in understanding the neuromuscular demands and support future evaluations of stroke deficits.

Patient-Clinician Brain Response During Clinical Encounter and Pain Treatment.

The patient-clinician relationship is known to significantly affect the pain experience, as empathy, mutual trust and therapeutic alliance can significantly modulate pain perception and influence clinical therapy outcomes. The aim of the present study was to use an EEG hyperscanning setup to identify brain and behavioral mechanisms supporting the patient-clinician relationship while this clinical dyad is engaged in a therapeutic interaction. Our previous study applied fMRI hyperscanning to investigate whether brain concordance is linked with analgesia experienced by a patient while undergoing treatment by the clinician. In this current hyperscanning project we investigated similar outcomes for the patient-clinician dyad exploiting the high temporal resolution of EEG and the possibility to acquire the signals while patients and clinicians were present in the same room and engaged in a face-to-face interaction under an experimentally-controlled therapeutic context. Advanced source localization methods allowed for integration of spatial and spectral information in order to assess brain correlates of therapeutic alliance and pain perception in different clinical interaction contexts. Preliminary results showed that both behavioral and brain responses across the patient-clinician dyad were significantly affected by the interaction style.Clinical Relevance- The context of a clinical intervention can significantly impact the treatment of chronic pain. Effective therapeutic alliance, based on empathy, mutual trust, and warmth can improve treatment adherence and clinical outcomes. A deeper scientific understanding of the brain and behavioral mechanisms underlying an optimal patient-clinician interaction may lead to improved quality of clinical care and physician training, as well as better understanding of the social aspects of the biopsychosocial model mediating analgesia in chronic pain patients.

Multiple-Brain Connectivity During Third Party Punishment: an EEG Hyperscanning Study.

Compassion is a particular form of empathic reaction to harm that befalls others and is accompanied by a desire to alleviate their suffering. This altruistic behavior is often manifested through altruistic punishment, wherein individuals penalize a deprecated human's actions, even if they are directed toward strangers. By adopting a dual approach, we provide empirical evidence that compassion is a multifaceted prosocial behavior and can predict altruistic punishment. In particular, in this multiple-brain connectivity study in an EEG hyperscanning setting, compassion was examined during real-time social interactions in a third-party punishment (TPP) experiment. We observed that specific connectivity patterns were linked to behavioral and psychological intra- and interpersonal factors. Thus, our results suggest that an ecological approach based on simultaneous dual-scanning and multiple-brain connectivity is suitable for analyzing complex social phenomena.

Brain connectivity networks at the basis of human attention components: An EEG study.

The Attention Network Task (ANT) was developed to disentangle the three components of attention identified in the Posner's theoretical model (alerting, orienting and executive control) and to measure the corresponding behavioral efficiency. Several fMRI studies have already provided evidences on the anatomical separability and interdependency of these three networks, and EEG studies have also unveiled the associated brain rhythms. What is still missing is a characterization of the brain circuits subtending the attentional components in terms of directed relationships between the brain areas and their frequency content. Here, we want to exploit the high temporal resolution of the EEG, improving its spatial resolution by means of advanced source localization methods, and to integrate the resulting information by a directed connectivity analysis. The results showed in the present study demonstrate the possibility to associate a specific directed brain circuit to each attention component and to identify synthetic indices able to selectively describe their neurophysiological, spatial and spectral properties.

Interfacing brain with computer to improve communication and rehabilitation after brain damage.

Communication and control of the external environment can be provided via brain-computer interfaces (BCIs) to replace a lost function in persons with severe diseases and little or no chance of recovery of motor abilities (ie, amyotrophic lateral sclerosis, brainstem stroke). BCIs allow to intentionally modulate brain activity, to train specific brain functions, and to control prosthetic devices, and thus, this technology can also improve the outcome of rehabilitation programs in persons who have suffered from a central nervous system injury (ie, stroke leading to motor or cognitive impairment). Overall, the BCI researcher is challenged to interact with people with severe disabilities and professionals in the field of neurorehabilitation. This implies a deep understanding of the disabled condition on the one hand, and it requires extensive knowledge on the physiology and function of the human brain on the other. For these reasons, a multidisciplinary approach and the continuous involvement of BCI users in the design, development, and testing of new systems are desirable. In this chapter, we will focus on noninvasive EEG-based systems and their clinical applications, highlighting crucial issues to foster BCI translation outside laboratories to eventually become a technology usable in real-life realm.

Measuring the agreement between brain connectivity networks.

Investigating the level of similarity between two brain networks, resulting from measures of effective connectivity in the brain, can be of interest from many respects. In this study, we propose and test the idea to borrow measures of association used in machine learning to provide a measure of similarity between the structure of (un-weighted) brain connectivity networks. The measures here explored are the accuracy, Cohen's Kappa (K) and Area Under Curve (AUC). We implemented two simulation studies, reproducing two contexts of application that can be particularly interesting for practical applications, namely: i) in methodological studies, performed on surrogate data, aiming at comparing the estimated network with the corresponding ground-truth network; ii) in applications to real data, when it is necessary to compare the structure of a network obtained in a specific subject with a reference (e.g. a baseline condition or normative data). In the simulations, the level of similarity between two networks was manipulated through different factors. We then investigated the effect of such manipulations on the measures of association. Results showed how the three parameters modulated their values according to the level of similarity between the two networks. In particular, the AUC provided the better performances in terms of its capability to synthetize the similarity between two networks, showing high dynamic and sensitivity.

Graph theory in brain-to-brain connectivity: A simulation study and an application to an EEG hyperscanning experiment.

Hyperscanning consists in the simultaneous recording of hemodynamic or neuroelectrical signals from two or more subjects acting in a social context. Well-established methodologies for connectivity estimation have already been adapted to hyperscanning purposes. The extension of graph theory approach to multi-subjects case is still a challenging issue. In the present work we aim to test the ability of the currently used graph theory global indices in describing the properties of a network given by two interacting subjects. The testing was conducted first on surrogate brain-to-brain networks reproducing typical social scenarios and then on real EEG hyperscanning data recorded during a Joint Action task. The results of the simulation study highlighted the ability of all the investigated indexes in modulating their values according to the level of interaction between subjects. However, only global efficiency and path length indexes demonstrated to be sensitive to an asymmetry in the communication between the two subjects. Such results were, then, confirmed by the application on real EEG data. Global efficiency modulated, in fact, their values according to the inter-brain density, assuming higher values in the social condition with respect to the non-social condition.

Effect of inter-trials variability on the estimation of cortical connectivity by Partial Directed Coherence.

Partial Directed Coherence (PDC) is a powerful estimator of effective connectivity. In neuroscience it is used in different applications with the aim to investigate the communication between brain regions during the execution of different motor or cognitive tasks. When multiple trials are available, PDC can be computed over multiple realizations, provided that the assumption of stationarity across trials is verified. This allows to improve the amount of data, which is an important constraint for the estimation accuracy. However, the stationarity of the data across trials is not always guaranteed, especially when dealing with patients. In this study we investigated how the inter-trials variability of an EEG dataset affects the PDC accuracy. Effects of density variations and of changes of connectivity values across trials were first investigated with a simulation study and then tested on real EEG data collected from two post-stroke patients during a motor imagery task and characterized by different inter-trials variability. Results showed the effect of different factors on the PDC accuracy and the robustness of such estimator in a range of conditions met in practical applications.

Investigating the effects of a sensorimotor rhythm-based BCI training on the cortical activity elicited by mental imagery.

OBJECTIVE: It is well known that to acquire sensorimotor (SMR)-based brain-computer interface (BCI) control requires a training period before users can achieve their best possible performances. Nevertheless, the effect of this training procedure on the cortical activity related to the mental imagery ability still requires investigation to be fully elucidated. The aim of this study was to gain insights into the effects of SMR-based BCI training on the cortical spectral activity associated with the performance of different mental imagery tasks. APPROACH: Linear cortical estimation and statistical brain mapping techniques were applied on high-density EEG data acquired from 18 healthy participants performing three different mental imagery tasks. Subjects were divided in two groups, one of BCI trained subjects, according to their previous exposure (at least six months before this study) to motor imagery-based BCI training, and one of subjects who were naive to any BCI paradigms. MAIN RESULTS: Cortical activation maps obtained for trained and naive subjects indicated different spectral and spatial activity patterns in response to the mental imagery tasks. Long-term effects of the previous SMR-based BCI training were observed on the motor cortical spectral activity specific to the BCI trained motor imagery task (simple hand movements) and partially generalized to more complex motor imagery task (playing tennis). Differently, mental imagery with spatial attention and memory content could elicit recognizable cortical spectral activity even in subjects completely naive to (BCI) training. SIGNIFICANCE: The present findings contribute to our understanding of BCI technology usage and might be of relevance in those clinical conditions when training to master a BCI application is challenging or even not possible.

Time varying effective connectivity for describing brain network changes induced by a memory rehabilitation treatment.

In clinical practice, cognitive impairment is often observed after stroke. The efficacy of rehabilitative interventions is routinely assessed by means of a neuropsychological test battery. Nowadays, more evidences indicate that the neuroplasticity which occurs after stroke can be better understood by investigating changes in brain networks. In this study we applied advanced methodologies for effective connectivity estimation in combination with graph theory approach, to define EEG derived descriptors of brain networks underlying memory tasks. In particular, we proposed such descriptors to identify substrates of efficacy of a Brain-Computer Interface (BCI) controlled neurofeedback intervention to improve cognitive function after stroke. Electroencephalographic (EEG) data were collected from two stroke patients before and after a neurofeedback-based training for memory deficits. We show that the estimated brain connectivity indices were sensitive to different training intervention outcomes, thus suggesting an effective support to the neuropsychological assessment in the evaluation of the changes induced by the BCI-based cognitive rehabilitative intervention.

A new descriptor of neuroelectrical activity during BCI-assisted motor imagery-based training in stroke patients.

In BCI applications for stroke rehabilitation, BCI systems are used with the aim of providing patients with an instrument that is capable of monitoring and reinforcing EEG patterns generated by motor imagery (MI). In this study we proposed an offline analysis on data acquired from stroke patients subjected to a BCI-assisted MI training in order to define an index for the evaluation of MI-BCI training session which is independent from the settings adopted for the online control and which is able to describe the properties of neuroelectrical activations across sessions. Results suggest that such index can be adopted to sort the trails within a session according to the adherence to the task.

Individual cortical connectivity changes after stroke: a resampling approach to enable statistical assessment at single-subject level.

One of the main limitations commonly encountered when dealing with the estimation of brain connectivity is the difficulty to perform a statistical assessment of significant changes in brain networks at a single-subject level. This is mainly due to the lack of information about the distribution of the connectivity estimators at different conditions. While group analysis is commonly adopted to perform a statistical comparison between conditions, it may impose major limitations when dealing with the heterogeneity expressed by a given clinical condition in patients. This holds true particularly for stroke when seeking for quantitative measurements of the efficacy of any rehabilitative intervention promoting recovery of function. The need is then evident of an assessment which may account for individual pathological network configuration associated with different level of patients' response to treatment; such network configuration is highly related to the effect that a given brain lesion has on neural networks. In this study we propose a resampling-based approach to the assessment of statistically significant changes in cortical connectivity networks at a single subject level. First, we provide the results of a simulation study testing the performances of the proposed approach under different conditions. Then, to show the sensitivity of the method, we describe its application to electroencephalographic (EEG) data recorded from two post-stroke patients who showed different clinical recovery after a rehabilitative intervention.

Investigating the neural basis of cooperative joint action. An EEG hyperscanning study.

The aim of the present study is to investigate the neurophysiological basis of the cognitive functions underlying the execution of joint actions, by means of the recent technique called hyperscanning. Neuroelectrical hyperscanning is based on the simultaneous recording of brain activity from multiple subjects and includes the analysis of the functional relation between the brain activity of all the interacting individuals. We recorded simultaneous high density electroencephalography (hdEEG) from 16 pairs of subjects involved in a computerized joint action paradigm, with controlled levels of cooperation. Results of cortical connectivity analysis returned significant differences, in terms of inter-brain functional causal links, between the condition of cooperative joint action and a condition in which the subjects were told they were interacting with a PC, while actually interacting with another human subject. Such differences, described by selected brain connectivity indices, point toward an integration between the two subjects' brain activity in the cooperative condition, with respect to control conditions.

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.

The effect of normalization of Partial Directed Coherence on the statistical assessment of connectivity patterns: a simulation study.

Partial Directed Coherence (PDC) is a spectral multivariate estimator for effective connectivity, relying on the concept of Granger causality. Even if its original definition derived directly from information theory, two modifies were introduced in order to provide better physiological interpretations of the estimated networks: i) normalization of the estimator according to rows, ii) squared transformation. In the present paper we investigated the effect of PDC normalization on the performances achieved by applying the statistical validation process on investigated connectivity patterns under different conditions of Signal to Noise ratio (SNR) and amount of data available for the analysis. Results of the statistical analysis revealed an effect of PDC normalization only on the percentages of type I and type II errors occurred by using Shuffling procedure for the assessment of connectivity patterns. No effects of the PDC formulation resulted on the performances achieved during the validation process executed instead by means of Asymptotic Statistic approach. Moreover, the percentages of both false positives and false negatives committed by Asymptotic Statistic are always lower than those achieved by Shuffling procedure for each type of normalization.

Aged-related changes in brain activity classification with respect to age by means of graph indexes.

Recent studies have investigated changes in the human brain network organization during the normal aging. A reduction of the connectivity between brain areas was demonstrated by combining neuroimaging technologies and graph theory. Clustering, characteristic path length and small-worldness are key topological measures and they are widely used in literature. In this paper we propose a new methodology that combine advanced techniques of effective connectivity estimation, graph theoretical approach and classification by SVM method. EEG signals recording during rest condition from 20 young subjects and 20 mid-aged adults were studied. Partial Directed Coherence was computed by means of General Linear Kalman Filter and graph indexes were extracted from estimated patterns. At last small-worldness was used as feature for the SVM classifier. Results show that topological differences of brain networks exist between young and mid-aged adults: small-worldness is significantly different between the two populations and it can be used to classify the subjects with respect to age with an accuracy of 69%.

Frontal EEG theta changes assess the training improvements of novices in flight simulation tasks.

The aim of the study is to analyze the variation of the EEG power spectra in theta band when a novice starts to learn a new task. In particular, the goal is to find out the differences from the beginning of the training to the session in which the performance level is good enough for considering him/her able to complete the task without any problems. While the novices were engaged in the flight simulation tasks we recorded the brain activity by using high resolution EEG techniques as well as neurophysiologic variables such as heart rate (HR) and eye blinks rate (EBR). Results show clear changes in the EEG power spectra in theta band over the frontal brain areas, either over the left, the midline and the right side, during the learning process of the task. These results are also supported by the autonomic signals of HR and EBR, by the performances' trends and by the questionnaires for the evaluation of the perceived workload level.