The humanoid robot WE4-RII was designed to express human emotions in order to improve human-robot interaction. We can read the emotions depicted in its gestures, yet might utilize different neural processes than those used for reading the emotions in human agents.

Benign childhood epilepsy with centrotemporal spikes (BECTS) has been investigated through EEG-fMRI with the aim of localizing the generators of the epileptic activity, revealing, in most cases, the activation of the sensory-motor cortex ipsilateral to the centrotemporal spikes (CTS). In this case report, we investigated the brain circuits hemodynamically involved by CTS recorded during wakefulness and sleep in one boy with CTS and a language disorder but without epilepsy. For this purpose, the patient underwent EEG-fMRI coregistration. During the "awake session", fMRI analysis of right-sided CTS showed increments of BOLD signal in the bilateral sensory-motor cortex. During the "sleep session", BOLD increments related to right-sided CTS were observed in a widespread bilateral cortical-subcortical network involving the thalamus, basal ganglia, sensory-motor cortex, perisylvian cortex, and cerebellum. In this patient, who fulfilled neither the diagnostic criteria for BECTS nor that for electrical status epilepticus in sleep (ESES), the transition from wakefulness to sleep was related to the involvement of a widespread cortical-subcortical network related to CTS. In particular, the involvement of a thalamic-perisylvian neural network similar to the one previously observed in patients with ESES suggests a common sleep-related network dysfunction even in cases with milder phenotypes without seizures. This finding, if confirmed in a larger cohort of patients, could have relevant therapeutic implication.

Evidence that the human premotor cortex (PMC) is activated by cognitive functions involving the motor domain is classically explained as the reactivation of a motor program decoupled from its executive functions, and exploited for different purposes by means of a motor simulation. In contrast, the evidence that PMC contributes to the sequencing of non-biological events cannot be explained by the simulationist theory. Here we investigated how motor simulation and event sequencing coexist within the PMC and how these mechanisms interact when both functions are executed. We asked patients with depth electrodes implanted in the PMC to passively observe a randomized arrangement of images depicting biological actions and physical events and, in a second block, to sequence them in the correct order. This task allowed us to disambiguate between the simple observation of actions, their sequencing (recruiting different motor simulation processes), as well as the sequencing of non-biological events (recruiting a sequencer mechanism non dependant on motor simulation). We analysed the response of the gamma, alpha and beta frequency bands to evaluate the contribution of each brain rhythm to the observation and sequencing of both biological and non-biological stimuli. We found that motor simulation (biological>physical) and event sequencing (sequencing>observation) differently affect the three investigated frequency bands: motor simulation was reflected on the gamma and, partially, in the beta, but not in the alpha band. In contrast, event sequencing was also reflected on the alpha band.

Melanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer disease (AD). We investigated mRGCs in AD, hypothesizing that they contribute to circadian dysfunction.

Williams syndrome (WS) is a rare genetic disorder associated with unusually hyper-social demeanor and ease with strangers. These personality traits are accompanied by difficulties in social interactions, possibly related, at least in part, to a difficulty in understanding others' mental states. Studies on mentalizing capacities in individuals with WS have often led to contrasting results, some studies revealing specific impairments, others highlighting spared mentalizing capacities. So far, however, no study investigated the performance of individuals with WS in non-inferential understanding of others' motor intentions. In the present study we investigated this capacity by using a computer-based behavioral task using pictures of hand-object interactions. We asked individuals with WS first to describe what the other was doing (i.e. a task implying no kind of intention reading), and secondly, if successful in answering the first question, to describe the motor intention underlying the observed motor acts (i.e. why an act was being done, a task requiring non-inferential motor intention understanding). Results showed that individuals with WS made more errors in understanding what the other was doing (i.e. understanding a motor act) compared to both mental-age matched controls and chronological-age matched peers with typical development, while showing mental-age appropriate performance in understanding why an individual was acting (i.e. understanding a motor intention). These findings suggest novel perspectives for understanding impairments in social behavior in WS.

Precisely localizing the sources of brain activity as recorded by EEG is a fundamental procedure and a major challenge for both research and clinical practice. Even though many methods and algorithms have been proposed, their relative advantages and limitations are still not well established. Moreover, these methods involve tuning multiple parameters, for which no principled way of selection exists yet. These uncertainties are emphasized due to the lack of ground-truth for their validation and testing. Here we present the Localize-MI dataset, which constitutes the first open dataset that comprises EEG recorded electrical activity originating from precisely known locations inside the brain of living humans. High-density EEG was recorded as single-pulse biphasic currents were delivered at intensities ranging from 0.1 to 5 mA through stereotactically implanted electrodes in diverse brain regions during pre-surgical evaluation of patients with drug-resistant epilepsy. The uses of this dataset range from the estimation of in vivo tissue conductivity to the development, validation and testing of forward and inverse solution methods.

During action observation, several visual features of observed actions can modulate the level of sensorimotor reactivity in the onlooker. Among possibly relevant parameters, one of the less investigated in humans is the visual perspective from which actions are observed. In the present EEG study, we assessed the reactivity of alpha and beta mu rhythm subcomponents to four different visual perspectives, defined by the position of the observer relative to the moving agent (identifying first-person, third-person and lateral viewpoints) and by the anatomical compatibility of observed effectors with self- or other individual's body (identifying ego- and allo-centric viewpoints, respectively). Overall, the strongest sensorimotor responsiveness emerged for first-person perspective. Furthermore, we found different patterns of perspective-dependent reactivity in rolandic alpha and beta ranges, with the former tuned to visuospatial details of observed actions and the latter tuned to action-related parameters (such as the direction of actions relative to the observer), suggesting a higher recruitment of beta motor rhythm in face-to-face interactions. The impact of these findings on the selection of most effective action stimuli for "Action Observation Treatment" neurorehabilitative protocols is discussed.

In a previous functional magnetic resonance imaging (fMRI) study, where we investigated the neural correlates of esthetic experience, we found that observing canonical sculptures, relative to sculptures whose proportions had been modified, produced the activation of a network that included the lateral occipital gyrus, precuneus, prefrontal areas, and, most interestingly, the right anterior insula. We interpreted this latter activation as the neural signature underpinning hedonic response during esthetic experience. With the aim of exploring whether this specific hedonic response is also present during the observation of non-art biological stimuli, in the present fMRI study we compared the activations associated with viewing masterpieces of classical sculpture with those produced by the observation of pictures of young athletes. The two stimulus-categories were matched on various factors, including body postures, proportion, and expressed dynamism. The stimuli were presented in two conditions: observation and esthetic judgment. The two stimulus-categories produced a rather similar global activation pattern. Direct comparisons between sculpture and real-body images revealed, however, relevant differences, among which the activation of right antero-dorsal insula during sculptures viewing only. Along with our previous data, this finding suggests that the hedonic state associated with activation of right dorsal anterior insula underpins esthetic experience for artworks.

What neural mechanism underlies the capacity to understand the emotions of others? Does this mechanism involve brain areas normally involved in experiencing the same emotion? We performed an fMRI study in which participants inhaled odorants producing a strong feeling of disgust. The same participants observed video clips showing the emotional facial expression of disgust. Observing such faces and feeling disgust activated the same sites in the anterior insula and to a lesser extent in the anterior cingulate cortex. Thus, as observing hand actions activates the observer's motor representation of that action, observing an emotion activates the neural representation of that emotion. This finding provides a unifying mechanism for understanding the behaviors of others.

Childhood epilepsy with centrotemporal spikes (CECTS) is the most common type of "self-limited focal epilepsies." In its typical presentation, CECTS is a condition reflecting non-lesional cortical hyperexcitability of rolandic regions. The benign evolution of this disorder is challenged by the frequent observation of associated neuropsychological deficits and behavioral impairment. The abundance (or frequency) of interictal centrotemporal spikes (CTS) in CECTS is considered a risk factor for deficits in cognition. Herein, we captured the hemodynamic changes triggered by the CTS density measure (i.e., the number of CTS for time bin) obtained in a cohort of CECTS, studied by means of video electroencephalophy/functional MRI during quite wakefulness. We aim to demonstrate a direct influence of the diurnal CTS frequency on epileptogenic and cognitive networks of children with CECTS. A total number of 8,950 CTS (range between 27 and 801) were recorded in 23 CECTS (21 male), with a mean number of 255 CTS/patient and a mean density of CTS/30 s equal to 10,866 ± 11.46. Two independent general linear model models were created for each patient based on the effect of interest: "individual CTS" in model 1 and "CTS density" in model 2. Hemodynamic correlates of CTS density revealed the involvement of a widespread cortical-subcortical network encompassing the sensory-motor cortex, the Broca's area, the premotor cortex, the thalamus, the putamen, and red nucleus, while in the CTS event-related model, changes were limited to blood-oxygen-level-dependent (BOLD) signal increases in the sensory-motor cortices. A linear relationship was observed between the CTS density hemodynamic changes and both disease duration (positive correlation) and age (negative correlation) within the language network and the bilateral insular cortices. Our results strongly support the critical role of the CTS frequency, even during wakefulness, to interfere with the normal functioning of language brain networks.

The properties of the secondary somatosensory area (SII) have been described by many studies in monkeys and humans. Recent studies on monkeys, however, showed that beyond somatosensory stimuli, SII responds to a wider number of stimuli, a finding requiring a revision that human SII is purely sensorimotor. By recording cortical activity with stereotactic electroencephalography (stereo-EEG), we examined the properties of SI and SII in response to a motor task requiring reaching, grasping and manipulation, as well as the observation of the same actions. Furthermore, we functionally characterized this area with a set of clinical tests, including tactile, acoustical, and visual stimuli. The results showed that only SII activates both during execution and observation with a common temporal profile, whereas SI response were limited to execution. Together with their peculiar response to tactile stimuli, we conclude that the role of SII is pivotal also in the observation of actions involving haptic control.

The processing steps that lead up to a decision, i.e., the transformation of sensory evidence into motor output, are not fully understood. Here, we combine stereoEEG recordings from the human cortex, with single-lead and time-resolved decoding, using a wide range of temporal frequencies, to characterize decision processing during a rule-switching task. Our data reveal the contribution of rostral inferior parietal lobule (IPL) regions, in particular PFt, and the parietal opercular regions in decision processing and demonstrate that the network representing the decision is common to both task rules. We reconstruct the sequence in which regions engage in decision processing on single trials, thereby providing a detailed picture of the network dynamics involved in decision-making. The reconstructed timeline suggests that the supramarginal gyrus in IPL links decision regions in prefrontal cortex with premotor regions, where the motor plan for the response is elaborated.

The perspective from which body-related stimuli are observed plays a fundamental role in modulating cerebral activity during the processing of others' bodies and actions. Previous research has shown perspective-dependent cerebral responses during the observation of both ongoing actions and static images of an acting body with implied motion information, with an advantage for the egocentric viewpoint. The present high-density EEG study assessed event-related potentials triggered by the presentation of a forearm at rest before reach-to-grasp actions, shown from four different viewpoints. Through a spatiotemporal analysis of the scalp electric field and the localization of cortical generators, our study revealed overall different processing for the third-person perspective relative to other viewpoints, mainly due to a later activation of motor-premotor regions. Since observing a static body effector often precedes action observation, our results integrate previous evidence of perspective-dependent encoding, with cascade implications on the design of neurorehabilitative or motor learning interventions based on action observation.

Previous studies showed that the understanding of others' basic emotional experiences is based on a "resonant" mechanism, i.e., on the reactivation, in the observer's brain, of the cerebral areas associated with those experiences. The present study aimed to investigate whether the same neural mechanism is activated both when experiencing and attending complex, cognitively-generated, emotions. A gambling task and functional-Magnetic-Resonance-Imaging (fMRI) were used to test this hypothesis using regret, the negative cognitively-based emotion resulting from an unfavorable counterfactual comparison between the outcomes of chosen and discarded options. Do the same brain structures that mediate the experience of regret become active in the observation of situations eliciting regret in another individual? Here we show that observing the regretful outcomes of someone else's choices activates the same regions that are activated during a first-person experience of regret, i.e. the ventromedial prefrontal cortex, anterior cingulate cortex and hippocampus. These results extend the possible role of a mirror-like mechanism beyond basic emotions.

Laughter is a complex motor behavior that, typically, expresses mirth. Despite its fundamental role in social life, knowledge about the neural basis of laughter is very limited and mostly based on a few electrical stimulation (ES) studies carried out in epileptic patients. In these studies laughter was elicited from temporal areas where it was accompanied by mirth and from frontal areas plus an anterior cingulate case where laughter without mirth was observed. On the basis of these findings, it has been proposed a dichotomy between temporal lobe areas processing the emotional content of laughter and anterior cingulate cortex (ACC) and motor areas responsible of laughter production. The present study is aimed to understand the role of ACC in laughter. We report the effects of stimulation of 10 rostral, pregenual ACC (pACC) patients in which the ES elicited laughter. In half of the patients ES elicited a clear burst of laughter with mirth, while in the other half mirth was not evident. This large dataset allow us to offer a more reliable picture of the functional contribute of this region in laughter, and to precisely localize it in the cingulate cortex. We conclude that the pACC is involved in both the motor and the affective components of emotions, and challenge the validity of a sharp dichotomy between motor and emotional centers for laughing. Finally, we suggest a possible anatomical network for the production of positive emotional expressions.

There is rich clinical evidence that observing normally executed actions promotes the recovery of the corresponding action execution in patients with motor deficits. In this study, we assessed the ability of action observation to prevent the decay of healthy individuals' motor abilities following upper-limb immobilization. To this end, upper-limb kinematics was recorded in healthy participants while they performed three reach-to-grasp movements before immobilization and the same movements after 16 h of immobilization. The participants were subdivided into two groups; the experimental group observed, during the immobilization, the same reach-to-grasp movements they had performed before immobilization, whereas the control group observed natural scenarios. After bandage removal, motor impairment in performing reach-to-grasp movements was milder in the experimental group. These findings support the hypothesis that action observation, via the mirror mechanism, plays a protective role against the decline of motor performance induced by limb nonuse. From this perspective, action observation therapy is a promising tool for anticipating rehabilitation onset in clinical conditions involving limb nonuse, thus reducing the burden of further rehabilitation.

Deidentifying MRIs constitutes an imperative challenge, as it aims at precluding the possibility of re-identification of a research subject or patient, but at the same time it should preserve as much geometrical information as possible, in order to maximize data reusability and to facilitate interoperability. Although several deidentification methods exist, no comprehensive and comparative evaluation of deidentification performance has been carried out across them. Moreover, the possible ways these methods can compromise subsequent analysis has not been exhaustively tested. To tackle these issues, we developed AnonyMI, a novel MRI deidentification method, implemented as a user-friendly 3D Slicer plugin-in, which aims at providing a balance between identity protection and geometrical preservation. To test these features, we performed two series of analyses on which we compared AnonyMI to other two state-of-the-art methods, to evaluate, at the same time, how efficient they are at deidentifying MRIs and how much they affect subsequent analyses, with particular emphasis on source localization procedures. Our results show that all three methods significantly reduce the re-identification risk but AnonyMI provides the best geometrical conservation. Notably, it also offers several technical advantages such as a user-friendly interface, multiple input-output capabilities, the possibility of being tailored to specific needs, batch processing and efficient visualization for quality assurance.

Since the second-half of the twentieth century, intracranial electroencephalography (iEEG), including both electrocorticography (ECoG) and stereo-electroencephalography (sEEG), has provided an intimate view into the human brain. At the interface between fundamental research and the clinic, iEEG provides both high temporal resolution and high spatial specificity but comes with constraints, such as the individual's tailored sparsity of electrode sampling. Over the years, researchers in neuroscience developed their practices to make the most of the iEEG approach. Here we offer a critical review of iEEG research practices in a didactic framework for newcomers, as well addressing issues encountered by proficient researchers. The scope is threefold: (i) review common practices in iEEG research, (ii) suggest potential guidelines for working with iEEG data and answer frequently asked questions based on the most widespread practices, and (iii) based on current neurophysiological knowledge and methodologies, pave the way to good practice standards in iEEG research. The organization of this paper follows the steps of iEEG data processing. The first section contextualizes iEEG data collection. The second section focuses on localization of intracranial electrodes. The third section highlights the main pre-processing steps. The fourth section presents iEEG signal analysis methods. The fifth section discusses statistical approaches. The sixth section draws some unique perspectives on iEEG research. Finally, to ensure a consistent nomenclature throughout the manuscript and to align with other guidelines, e.g., Brain Imaging Data Structure (BIDS) and the OHBM Committee on Best Practices in Data Analysis and Sharing (COBIDAS), we provide a glossary to disambiguate terms related to iEEG research.

The objective of the present work was to identify electroencephalographic (EEG) components in order to distinguish between braking and accelerating intention in simulated car driving. To do so, we collected high-density EEG data from thirty participants while they were driving in a car simulator. The EEG was separated into independent components that were clustered across participants according to their scalp map topographies. For each component, time-frequency activity related to braking and acceleration events was determined through wavelet analysis, and the cortical generators were estimated through minimum norm source localisation. Comparisons of the time-frequency patterns of power and phase activations revealed that theta power synchronisation distinguishes braking from acceleration events 800 ms before the action and that phase-locked activity increases for braking 800 ms before foot movement in the theta-alpha frequency range. In addition, source reconstruction showed that the dorso-mesial part of the premotor cortex plays a key role in preparation of foot movement. Overall, the results illustrate that dorso-mesial premotor areas are involved in movement preparation while driving, and that low-frequency EEG rhythms could be exploited to predict drivers' intention to brake or accelerate.

In Alzheimer's disease (AD), the presence of circadian dysfunction is well-known and may occur early in the disease course. The melanopsin retinal ganglion cell (mRGC) system may play a relevant role in contributing to circadian dysfunction. In this study, we aimed at evaluating, through a multimodal approach, the mRGC system in AD at an early stage of disease.