Sleep Spindle Generation Before and After Epilepsy Surgery: A Source Imaging Study in Children with Drug-Resistant Epilepsy.

INTRODUCTION: Literature lacks studies investigating the cortical generation of sleep spindles in drug-resistant epilepsy (DRE) and how they evolve after resection of the epileptogenic zone (EZ). Here, we examined sleep EEGs of children with focal DRE who became seizure-free after focal epilepsy surgery, and aimed to investigate the changes in the spindle generation before and after the surgery using low-density scalp EEG and electrical source imaging (ESI). METHODS: We analyzed N2-sleep EEGs from 19 children with DRE before and after surgery. We identified slow (8-12 Hz) and fast spindles (13-16 Hz), computed their spectral features and cortical generators through ESI and computed their distance from the EZ and irritative zone (IZ). We performed two-way ANOVA testing the effect of spindle type (slow vs. fast) and surgical phase (pre-surgery vs. post-surgery) on each feature. RESULTS: Power, frequency and cortical activation of slow spindles increased after surgery (p < 0.005), while this was not seen for fast spindles. Before surgery, the cortical generators of slow spindles were closer to the EZ (57.3 vs. 66.2 mm, p = 0.007) and IZ (41.3 vs. 55.5 mm, p = 0.02) than fast spindle generators. CONCLUSIONS: Our data indicate alterations in the EEG slow spindles after resective epilepsy surgery. Fast spindle generation on the contrary did not change after surgery. Although the study is limited by its retrospective nature, lack of healthy controls, and reduced cortical spatial sampling, our findings suggest a spatial relationship between the slow spindles and the epileptogenic generators.

Reaching While Learning to Sit: Capturing the Kinematics of Co-Developing Skills at Home.

This study examined the co-development of infant reaching and postural control across the transition to arms-free sitting at home. We observed infants with typical likelihood (TL; n = 24) and elevated likelihood (EL; n = 20) for autism at four biweekly sessions spanning the transition to arms-free sitting (infant age = 4.5-8 months at first session). At each session, infants sat on a pressure-sensitive mat with external support or independently, wore magneto-inertial sensors on both wrists, and reached for toys presented at midline. Analyses focused on characterizing and comparing control of sitting during reaching actions and standard kinematic metrics of reaching during Supported versus Independent Sitting. Although EL infants achieved arms-free sitting later than TL peers, there were no group differences on any measures. Across sessions, infants' control of the sitting posture during concurrent reaching movements improved in both contexts, though they were less stable as they reached when sitting independently compared to when sitting with support. A similar effect was apparent in the kinematics of reaches, with overall improvement over time, but evidence of poorer control in Independent relative to Supported Sitting. Taken together, these findings underscore the mutually influential and dynamic relations between emerging skills and well-established behaviors.

Real-Time Visual Feedback Based on MIMUs Technology Reduces Bowing Errors in Beginner Violin Students.

Violin is one of the most complex musical instruments to learn. The learning process requires constant training and many hours of exercise and is primarily based on a student-teacher interaction where the latter guides the beginner through verbal instructions, visual demonstrations, and physical guidance. The teacher's instruction and practice allow the student to learn gradually how to perform the correct gesture autonomously. Unfortunately, these traditional teaching methods require the constant supervision of a teacher and the interpretation of non-real-time feedback provided after the performance. To address these limitations, this work presents a novel interface (Visual Interface for Bowing Evaluation-VIBE) to facilitate student's progression throughout the learning process, even in the absence of direct teacher intervention. The proposed interface allows two key parameters of bowing movements to be monitored, namely, the angle between the bow and the string (i.e., α angle) and the bow tilt (i.e., ß angle), providing real-time visual feedback on how to correctly move the bow. Results collected on 24 beginners (12 exposed to visual feedback, 12 in a control group) showed a positive effect of the real-time visual feedback on the improvement of bow control. Moreover, the subjects exposed to visual feedback judged the latter as useful to correct their movement and clear in terms of the presentation of data. Although the task was rated as harder when performed with the additional feedback, the subjects did not perceive the presence of a violin teacher as essential to interpret the feedback.

Assessing the Bowing Technique in Violin Beginners Using MIMU and Optical Proximity Sensors: A Feasibility Study.

Bowing is the fundamental motor action responsible for sound production in violin playing. A lot of effort is required to control such a complex technique, especially at the beginning of violin training, also due to a lack of quantitative assessments of bowing movements. Here, we present magneto-inertial measurement units (MIMUs) and an optical sensor interface for the real-time monitoring of the fundamental parameters of bowing. Two MIMUs and a sound recorder were used to estimate the bow orientation and acquire sounds. An optical motion capture system was used as the gold standard for comparison. Four optical sensors positioned on the bow stick measured the stick-hair distance. During a pilot test, a musician was asked to perform strokes using different sections of the bow at different paces. Distance data were used to train two classifiers, a linear discriminant (LD) classifier and a decision tree (DT) classifier, to estimate the bow section used. The DT classifier reached the best classification accuracy (94.2%). Larger data analysis on nine violin beginners showed that the orientation error was less than 2°; the bow tilt correlated with the audio information (r134=-0.973, 95% CI -0.981,-0.962,  p<0.001). The results confirmed that the interface provides reliable information on the bowing technique that might improve the learning performance of violin beginners.

Embodying melody through a conducting baton: a pilot comparison between musicians and non-musicians.

Finger-tapping tasks have been widely adopted to investigate auditory-motor synchronization, i.e., the coupling of movement with an external auditory rhythm. However, the discrete nature of these movements usually limits their application to the study of beat perception in the context of isochronous rhythms. The purpose of the present pilot study was to test an innovative task that allows investigating bodily responses to complex, non-isochronous rhythms. A conductor's baton was provided to 16 healthy subjects, divided into 2 different groups depending on the years of musical training they had received (musicians or non-musicians). Ad hoc-created melodies, including notes of different durations, were played to the subjects. Each subject was asked to move the baton up and down according to the changes in pitch contour. Software for video analysis and modelling (Tracker®) was used to track the movement of the baton tip. The main parameters used for the analysis were the velocity peaks in the vertical axis. In the musician group, the number of velocity peaks exactly matched the number of notes, while in the non-musician group, the number of velocity peaks exceeded the number of notes. An exploratory data analysis using Poincaré plots suggested a greater degree of coupling between hand-arm movements and melody in musicians both with isochronous and non-isochronous rhythms. The calculated root mean square error (RMSE) between the note onset times and the velocity peaks, and the analysis of the distribution of velocity peaks in relationship to note onset times confirmed the effect of musical training. Notwithstanding the small number of participants, these results suggest that this novel behavioural task could be used to investigate auditory-motor coupling in the context of music in an ecologically valid setting. Furthermore, the task may be used for rhythm training and rehabilitation in neurological patients with movement disorders.

Surgical resection of ripple onset predicts outcome in pediatric epilepsy.

OBJECTIVE: In patients with medically refractory epilepsy (MRE), interictal ripples (80-250Hz) are observed in large brain areas whose resection may be unnecessary for seizure freedom. This limits their utility as epilepsy biomarkers for surgery. We assessed the spatiotemporal propagation of interictal ripples on intracranial electroencephalography (iEEG) in children with MRE, compared it with the propagation of spikes, identified ripples that initiated propagation (onset-ripples), and evaluated their clinical value as epilepsy biomarkers. METHODS: Twenty-seven children who underwent epilepsy surgery were studied. We identified propagation sequences of ripples and spikes across multiple iEEG contacts and calculated each ripple or spike latency from the propagation onset. We classified ripples and spikes into categories (ie, onset, spread, and isolated) based on their spatiotemporal characteristics and correlated their mean rate inside and outside resection with outcome (good outcome, Engel 1 versus poor outcome, Engel≥2). We determined, as onset-zone, spread-zone, and isolated-zone, the areas generating the corresponding ripple or spike category and evaluated the predictive value of their resection. RESULTS: We observed ripple propagation in all patients and spike propagation in 25 patients. Mean rate of onset-ripples inside resection predicted the outcome (odds ratio = 5.37; p = 0.02) and correlated with Engel class (rho = -0.55; p = 0.003). Resection of the onset-ripple-zone was associated with good outcome (p = 0.047). No association was found for the spread-ripple-zone, isolated-ripple-zone, or any spike-zone. INTERPRETATION: Interictal ripples propagate across iEEG contacts in children with MRE. The association between the onset-ripple-zone resection and good outcome indicates that onset-ripples are promising epilepsy biomarkers, which estimate the epileptogenic tissue better than spread-ripples or onset-spikes. Ann Neurol 2018;84:331-346.

Performance Evaluation of Bluetooth Low Energy: A Systematic Review.

Small, compact and embedded sensors are a pervasive technology in everyday life for a wide number of applications (e.g., wearable devices, domotics, e-health systems, etc.). In this context, wireless transmission plays a key role, and among available solutions, Bluetooth Low Energy (BLE) is gaining more and more popularity. BLE merges together good performance, low-energy consumption and widespread diffusion. The aim of this work is to review the main methodologies adopted to investigate BLE performance. The first part of this review is an in-depth description of the protocol, highlighting the main characteristics and implementation details. The second part reviews the state of the art on BLE characteristics and performance. In particular, we analyze throughput, maximum number of connectable sensors, power consumption, latency and maximum reachable range, with the aim to identify what are the current limits of BLE technology. The main results can be resumed as follows: throughput may theoretically reach the limit of ~230 kbps, but actual applications analyzed in this review show throughputs limited to ~100 kbps; the maximum reachable range is strictly dependent on the radio power, and it goes up to a few tens of meters; the maximum number of nodes in the network depends on connection parameters, on the network architecture and specific device characteristics, but it is usually lower than 10; power consumption and latency are largely modeled and analyzed and are strictly dependent on a huge number of parameters. Most of these characteristics are based on analytical models, but there is a need for rigorous experimental evaluations to understand the actual limits.

Exploration and learning in capuchin monkeys (Sapajus spp.): the role of action-outcome contingencies.

Animals have a strong propensity to explore the environment. Spontaneous exploration has a great biological significance since it allows animals to discover and learn the relation between specific behaviours and their consequences. The role of the contingency between action and outcome for learning has been mainly investigated in instrumental learning settings and much less in free exploration contexts. We tested 16 capuchin monkeys (Sapajus spp.) with a mechatronic platform that allowed complex modules to be manipulated and to produce different outcomes. Experimental subjects could manipulate the modules and discover the contingencies between their own specific actions and the outcomes produced (i.e., the opening and lighting of a box). By contrast, Control subjects could operate on the modules, but the outcomes experienced were those performed by their paired Experimental subjects ("yoked-control" paradigm). In the exploration phase, in which no food reward was present, Experimental subjects spent more time on the board and manipulated the modules more than Yoked subjects. Experimental subjects outperformed Yoked subjects in the following test phase, where success required recalling the effective action so to open the box, now baited with food. These findings demonstrate that the opportunity to experience action-outcome contingencies in the absence of extrinsic rewards promotes capuchins' exploration and facilitates learning processes. Thus, this intrinsically motivated learning represents a powerful mechanism allowing the acquisition of skills and cognitive competence that the individual can later exploit for adaptive purposes.

Development of goal-directed action selection guided by intrinsic motivations: an experiment with children.

Action selection is extremely important, particularly when the accomplishment of competitive tasks may require access to limited motor resources. The spontaneous exploration of the world plays a fundamental role in the development of this capacity, providing subjects with an increasingly diverse set of opportunities to acquire, practice and refine the understanding of action-outcome connection. The computational modeling literature proposed a number of specific mechanisms for autonomous agents to discover and target interesting outcomes: intrinsic motivations hold a central importance among those mechanisms. Unfortunately, the study of the acquisition of action-outcome relation was mostly carried out with experiments involving extrinsic tasks, either based on rewards or on predefined task goals. This work presents a new experimental paradigm to study the effect of intrinsic motivation on action-outcome relation learning and action selection during free exploration of the world. Three- and four-year-old children were observed during the free exploration of a new toy: half of them were allowed to develop the knowledge concerning its functioning; the other half were not allowed to learn anything. The knowledge acquired during the free exploration of the toy was subsequently assessed and compared.

A new calibration methodology for thorax and upper limbs motion capture in children using magneto and inertial sensors.

Recent advances in wearable sensor technologies for motion capture have produced devices, mainly based on magneto and inertial measurement units (M-IMU), that are now suitable for out-of-the-lab use with children. In fact, the reduced size, weight and the wireless connectivity meet the requirement of minimum obtrusivity and give scientists the possibility to analyze children's motion in daily life contexts. Typical use of magneto and inertial measurement units (M-IMU) motion capture systems is based on attaching a sensing unit to each body segment of interest. The correct use of this setup requires a specific calibration methodology that allows mapping measurements from the sensors' frames of reference into useful kinematic information in the human limbs' frames of reference. The present work addresses this specific issue, presenting a calibration protocol to capture the kinematics of the upper limbs and thorax in typically developing (TD) children. The proposed method allows the construction, on each body segment, of a meaningful system of coordinates that are representative of real physiological motions and that are referred to as functional frames (FFs). We will also present a novel cost function for the Levenberg-Marquardt algorithm, to retrieve the rotation matrices between each sensor frame (SF) and the corresponding FF. Reported results on a group of 40 children suggest that the method is repeatable and reliable, opening the way to the extensive use of this technology for out-of-the-lab motion capture in children.

Technological solutions and main indices for the assessment of newborns' nutritive sucking: a review.

Nutritive Sucking (NS) is a highly organized process that is essential for infants' feeding during the first six months of their life. It requires the complex coordination of sucking, swallowing and breathing. The infant's inability to perform a safe and successful oral feeding can be an early detector of immaturity of the Central Nervous System (CNS). Even though the importance of early sucking measures has been confirmed over the years, the need for standardized instrumental assessment tools still exists. Clinicians would benefit from specifically designed devices to assess oral feeding ability in their routine clinical monitoring and decision-making process. This work is a review of the main instrumental solutions developed to assess an infant's NS behavior, with a detailed survey of the main quantities and indices measured and/or estimated to characterize sucking behavior skills and their development. The adopted sensing measuring systems will be described, and their main advantages and weaknesses will be discussed, taking into account their application to clinical practice, or to at-home monitoring as post-discharge assessment tools. Finally, the study will highlight the most suitable sensing solutions and give some prompts for further research.

Optical fiber-based MR-compatible sensors for medical applications: an overview.

During last decades, Magnetic Resonance (MR)--compatible sensors based on different techniques have been developed due to growing demand for application in medicine. There are several technological solutions to design MR-compatible sensors, among them, the one based on optical fibers presents several attractive features. The high elasticity and small size allow designing miniaturized fiber optic sensors (FOS) with metrological characteristics (e.g., accuracy, sensitivity, zero drift, and frequency response) adequate for most common medical applications; the immunity from electromagnetic interference and the absence of electrical connection to the patient make FOS suitable to be used in high electromagnetic field and intrinsically safer than conventional technologies. These two features further heightened the potential role of FOS in medicine making them especially attractive for application in MRI. This paper provides an overview of MR-compatible FOS, focusing on the sensors employed for measuring physical parameters in medicine (i.e., temperature, force, torque, strain, and position). The working principles of the most promising FOS are reviewed in terms of their relevant advantages and disadvantages, together with their applications in medicine.

Embedding inertial-magnetic sensors in everyday objects: assessing spatial cognition in children.

This paper describes an interdisciplinary approach to the assessment of children development of spatial cognition, with a focus on the technology. An instrumented toy (block-box) is presented which embeds magneto-inertial sensors for orientation tracking, specifically developed to assess the ability to insert objects into holes. The functional specifications are derived from experimental protocols devised by neuroscientists to assess spatial cognition skills in children. Technological choices are emphasized with respect to ecological requirements. Ad-hoc calibration procedures are presented which are suitable to unstructured environments. Preliminary results based on experimental trials carried out at a day-care on typically developing children (12-36 months old) show how the instrumented objects can be used effectively in a semi-automatic fashion (i.e., rater-independent) to derive accurate measurements such as orientation errors and insertion time which are relevant to the object insertion task. This study indicates that a technological approach to ecological assessment of spatial cognition in children is indeed feasible and maybe useful for identification and early assessment of developmental delay.

A mechatronic platform for behavioral analysis on nonhuman primates.

In this work we present a new mechatronic platform for measuring behavior of nonhuman primates, allowing high reprogrammability and providing several possibilities of interactions. The platform is the result of a multidisciplinary design process, which has involved bio-engineers, developmental neuroscientists, primatologists, and roboticians to identify its main requirements and specifications. Although such a platform has been designed for the behavioral analysis of capuchin monkeys (Cebus apella), it can be used for behavioral studies on other nonhuman primates and children. First, a state-of-the-art principal approach used in nonhuman primate behavioral studies is reported. Second, the main advantages of the mechatronic approach are presented. In this section, the platform is described in all its parts and the possibility to use it for studies on learning mechanism based on intrinsic motivation discussed. Third, a pilot study on capuchin monkeys is provided and preliminary data are presented and discussed.

Evaluating Handwriting Skills through Human-Machine Interaction: A New Digitalized System for Parameters Extraction.

Handwriting is an important component of academic curricula and grapho-motor skills (GMS) support learning, reading, memory and self-confidence. Teachers and clinicians report increase in children experiencing problems with acquiring fluid and legible handwriting. To date gold-standard tests evaluating children's GMS, mostly rely on pen and paper tests, requiring extensive coding time and subject to high inter-rater variability. This work presents preliminary data on a new digital platform for Grapho-motor Handwriting Evaluation & Exercise (GHEE), attempting to overcome limitations of available digitalized methods for GMS evalution. In fact, contrary to previous systems, GHEE design originated from comparisons among multiple standardized tests and was based on a human-machine interaction approach. GHEE hardware and software is presented as well as data on preliminary testing. Cursive handwriting data from six adult volunteers was analyzed according to six parameters of relevance, both automatically (i.e., using GHEE software) and manually (i.e., by a human coder). Comparisons among machine and human data sets allowed parsing out parameters to be extracted automatically and parameters requiring human-machine interaction. Results confirmed platform efficacy and feasibility of the proposed approach.

Novel User-Friendly Application for MRI Segmentation of Brain Resection following Epilepsy Surgery.

Delineation of resected brain cavities on magnetic resonance images (MRIs) of epilepsy surgery patients is essential for neuroimaging/neurophysiology studies investigating biomarkers of the epileptogenic zone. The gold standard to delineate the resection on MRI remains manual slice-by-slice tracing by experts. Here, we proposed and validated a semiautomated MRI segmentation pipeline, generating an accurate model of the resection and its anatomical labeling, and developed a graphical user interface (GUI) for user-friendly usage. We retrieved pre- and postoperative MRIs from 35 patients who had focal epilepsy surgery, implemented a region-growing algorithm to delineate the resection on postoperative MRIs and tested its performance while varying different tuning parameters. Similarity between our output and hand-drawn gold standards was evaluated via dice similarity coefficient (DSC; range: 0-1). Additionally, the best segmentation pipeline was trained to provide an automated anatomical report of the resection (based on presurgical brain atlas). We found that the best-performing set of parameters presented DSC of 0.83 (0.72-0.85), high robustness to seed-selection variability and anatomical accuracy of 90% to the clinical postoperative MRI report. We presented a novel user-friendly open-source GUI that implements a semiautomated segmentation pipeline specifically optimized to generate resection models and their anatomical reports from epilepsy surgery patients, while minimizing user interaction.

Changes in the Functional Brain Network of Children Undergoing Repeated Epilepsy Surgery: An EEG Source Connectivity Study.

About 30% of children with drug-resistant epilepsy (DRE) continue to have seizures after epilepsy surgery. Since epilepsy is increasingly conceptualized as a network disorder, understanding how brain regions interact may be critical for planning re-operation in these patients. We aimed to estimate functional brain connectivity using scalp EEG and its evolution over time in patients who had repeated surgery (RS-group, n = 9) and patients who had one successful surgery (seizure-free, SF-group, n = 12). We analyzed EEGs without epileptiform activity at varying time points (before and after each surgery). We estimated functional connectivity between cortical regions and their relative centrality within the network. We compared the pre- and post-surgical centrality of all the non-resected (untouched) regions (far or adjacent to resection) for each group (using the Wilcoxon signed rank test). In alpha, theta, and beta frequency bands, the post-surgical centrality of the untouched cortical regions increased in the SF group (p < 0.001) whereas they decreased (p < 0.05) or did not change (p > 0.05) in the RS group after failed surgeries; when re-operation was successful, the post-surgical centrality of far regions increased (p < 0.05). Our data suggest that removal of the epileptogenic focus in children with DRE leads to a gain in the network centrality of the untouched areas. In contrast, unaltered or decreased connectivity is seen when seizures persist after surgery.

Motor performance in a shape sorter task: A longitudinal study from 14 to 36 months of age in children with an older sibling ASD.

During development, motor skills are fundamental in supporting interactions with the external world. The ability to plan actions is a particularly important aspect of motor skill since it is involved in many daily activities. In this work, we studied the development of motor planning longitudinally in children with an older sibling with Autism Spectrum Disorder (ASD) who are at heightened risk (HR) for the disorder and children with no such risk (low risk; LR) using a shape sorter task. Children were observed at 14, 18, 24 and 36 months. Three HR children with a later diagnosis of ASD (HR-ASD) were analyzed separately from the rest of the sample. Behavioral and kinematic data indicated that precision demands significantly influenced children's actions, and that children's performance improved with age. No differences were found between the HR and LR groups, but a descriptive analysis of data from the three HR-ASD suggested differences in the variables describing children's action (as reaching time and acceleration) as well as variables describing children's performance (as the adjustment of the shapes).

Assessment of feeding teats: an experimental study.

This work aims to present a quantitative metric to assess the impact of feeding teats on the nutritive sucking of newborns. Two different teat models are compared: a classical model (model C), and a model provided with two opposite recesses to match the anatomical characteristics of the mouth of a newborn (model I). This latter feeding teat model has been specifically designed to promote the attachment of the baby, thus improving her/his nutritive sucking performance.Feeding teats are instrumented with a device to assess nutritive sucking (the Feeding Assessment Monitor, FAM). The device records feeding pressures and a software extracts quantitative features already used and validated in clinical applications.Comparative cross-over analysis on 30 healthy newborns, demonstrates the appropriateness of the proposed metric to reveal differences in the teat models. In particular, our data confirm the better attachment of newborns when fed with the I model: they show a longer feeding, with higher level of depressurization, higher regularity, and higher number of sucking events.

Nutritive sucking abnormalities and brain microstructural abnormalities in infants with established brain injury: a pilot study.

OBJECTIVE: To determine the relationship between nutritive sucking and microstructural integrity of sensorimotor tracts in newborns with brain injury. STUDY DESIGN: Diffusion imaging was performed in ten newborns with brain injury. Nutritive sucking was assessed using Nfant®. The motor, sensory, and corpus callosum tracts were reconstructed via tractography. Fractional anisotropy, radial, axial, and mean diffusivity were estimated for these tracts. Multiple regression models were developed to test the association between sucking features and diffusion parameters. RESULTS: Low-sucking smoothness correlated with low-fractional anisotropy of motor tracts (p = 0.0096). High-sucking irregularity correlated with high-mean diffusivity of motor (p = 0.030) and corpus callosum tracts (p = 0.032). For sensory tracts, high-sucking irregularity (p = 0.018) and low-smoothness variability (p = 0.002) correlated with high-mean diffusivity. INTERPRETATION: We show a correlation between neuroimaging-demonstrated microstructural brain abnormalities and variations in sucking patterns of newborns. The consistency of this relationship should be shown on larger cohorts.