Publications

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.

INTRODUCTION: This study evaluates magnetoencephalographic (MEG) spike population as compared with intracranial electroencephalographic (IEEG) spikes using a quantitative method based on distributed source analysis.

METHODS: We retrospectively studied eight patients with medically intractable epilepsy who had an MEG and subsequent IEEG monitoring. Fifty MEG spikes were analyzed in each patient using minimum norm estimate. For individual spikes, each vertex in the source space was considered activated when its source amplitude at the peak latency was higher than a threshold, which was set at 50% of the maximum amplitude over all vertices. We mapped the total count of activation at each vertex. We also analyzed 50 IEEG spikes in the same manner over the intracranial electrodes and created the activation count map. The location of the electrodes was obtained in the MEG source space by coregistering postimplantation computed tomography to MRI. We estimated the MEG- and IEEG-active regions associated with the spike populations using the vertices/electrodes with a count over 25.

RESULTS: The activation count maps of MEG spikes demonstrated the localization associated with the spike population by variable count values at each vertex. The MEG-active region overlapped with 65 to 85% of the IEEG-active region in our patient group.

CONCLUSIONS: Mapping the MEG spike population is valid for demonstrating the trend of spikes clustering in patients with epilepsy. In addition, comparison of MEG and IEEG spikes quantitatively may be informative for understanding their relationship.

BACKGROUND: The purpose of this study is to clarify the source distribution patterns of magnetoencephalographic spikes correlated with postsurgical seizure-free outcome in pediatric patients with focal cortical dysplasia.

PATIENTS AND METHODS: Thirty-two patients with pathologically confirmed focal cortical dysplasia were divided into seizure-free and seizure-persistent groups according to their surgical outcomes based on Engel classification. In each patient, presurgical magnetoencephalography was reviewed. Dipole sources of magnetoencephalographic spikes were calculated according to a single dipole model. We obtained the following quantitative indices for evaluating dipole distribution: maximum distance over all pairs of dipoles, standard deviation of the distances between each dipole and the mean coordinate of all dipoles, average nearest neighbor distance, the rate of dipoles located within 10, 20, and 30 mm from the mean coordinate, and the rate of dipoles included in the resection. These indices were compared between the two patient groups.

RESULTS: Average nearest neighbor distance was significantly smaller in the seizure-free group than in the seizure-persistent group (P = 0.008). The rates of dipoles located within 10, 20, and 30 mm from the mean coordinate were significantly higher in the seizure-free group (P = 0.001, 0.001, 0.005, respectively). The maximum distance, standard deviation, and resection rate of dipoles did not show a significant difference between the two groups.

CONCLUSIONS: A spatially restricted dipole distribution of magnetoencephalographic spikes is correlated with postsurgical seizure-free outcomes in patients with focal cortical dysplasia. The distribution can be assessed by quantitative indices that are clinically useful in the presurgical evaluation of these patients.

Neonatal feeding has been traditionally understudied so guidelines and evidence-based support for common feeding practices are limited. A major contributing factor to the paucity of evidence-based practice in this area has been the lack of simple-to-use, low-cost tools for monitoring sucking performance. We describe new methods for quantifying neonatal sucking performance that hold significant clinical and research promise. We present early results from an ongoing study investigating neonatal sucking as a marker of risk for adverse neurodevelopmental outcomes. We include quantitative measures of sucking performance to better understand how movement variability evolves during skill acquisition. Results showed the coefficient of variation of suck duration was significantly different between preterm neonates at high risk for developmental concerns (HRPT) and preterm neonates at low risk for developmental concerns (LRPT). For HRPT, results indicated the coefficient of variation of suck smoothness increased from initial feeding to discharge and remained significantly greater than healthy full-term newborns (FT) at discharge. There was no significant difference in our measures between FT and LRPT at discharge. Our findings highlight the need to include neonatal sucking assessment as part of routine clinical care in order to capture the relative risk of adverse neurodevelopmental outcomes at discharge.

Up to one-third of patients with epilepsy are medically intractable and need resective surgery. To be successful, epilepsy surgery requires a comprehensive preoperative evaluation to define the epileptogenic zone (EZ), the brain area that should be resected to achieve seizure freedom. Due to lack of tools and methods that measure the EZ directly, this area is defined indirectly based on concordant data from a multitude of presurgical non-invasive tests and intracranial recordings. However, the results of these tests are often insufficiently concordant or inconclusive. Thus, the presurgical evaluation of surgical candidates is frequently challenging or unsuccessful. To improve the efficacy of the surgical treatment, there is an overriding need for reliable biomarkers that can delineate the EZ. High-frequency oscillations (HFOs) have emerged over the last decade as new potential biomarkers for the delineation of the EZ. Multiple studies have shown that HFOs are spatially associated with the EZ. Despite the encouraging findings, there are still significant challenges for the translation of HFOs as epileptogenic biomarkers to the clinical practice. One of the major barriers is the difficulty to detect and localize them with non-invasive techniques, such as magnetoencephalography (MEG) or scalp electroencephalography (EEG). Although most literature has studied HFOs using invasive recordings, recent studies have reported the detection and localization of HFOs using MEG or scalp EEG. MEG seems to be particularly advantageous compared to scalp EEG due to its inherent advantages of being less affected by skull conductivity and less susceptible to contamination from muscular activity. The detection and localization of HFOs with MEG would largely expand the clinical utility of these new promising biomarkers to an earlier stage in the diagnostic process and to a wider range of patients with epilepsy. Here, we conduct a thorough critical review of the recent MEG literature that investigates HFOs in patients with epilepsy, summarizing the different methodological approaches and the main findings. Our goal is to highlight the emerging potential of MEG in the non-invasive detection and localization of HFOs for the presurgical evaluation of patients with medically refractory epilepsy (MRE).

Crucial to the success of epilepsy surgery is the availability of a robust biomarker that identifies the Epileptogenic Zone (EZ). High Frequency Oscillations (HFOs) have emerged as potential presurgical biomarkers for the identification of the EZ in addition to Interictal Epileptiform Discharges (IEDs) and ictal activity. Although they are promising to localize the EZ, they are not yet suited for the diagnosis or monitoring of epilepsy in clinical practice. Primary barriers remain: the lack of a formal and global definition for HFOs; the consequent heterogeneity of methodological approaches used for their study; and the practical difficulties to detect and localize them noninvasively from scalp recordings. Here, we present a methodology for the recording, detection, and localization of interictal HFOs from pediatric patients with refractory epilepsy. We report representative data of HFOs detected noninvasively from interictal scalp EEG and MEG from two children undergoing surgery. The underlying generators of HFOs were localized by solving the inverse problem and their localization was compared to the Seizure Onset Zone (SOZ) as this was defined by the epileptologists. For both patients, Interictal Epileptogenic Discharges (IEDs) and HFOs were localized with source imaging at concordant locations. For one patient, intracranial EEG (iEEG) data were also available. For this patient, we found that the HFOs localization was concordant between noninvasive and invasive methods. The comparison of iEEG with the results from scalp recordings served to validate these findings. To our best knowledge, this is the first study that presents the source localization of scalp HFOs from simultaneous EEG and MEG recordings comparing the results with invasive recordings. These findings suggest that HFOs can be reliably detected and localized noninvasively with scalp EEG and MEG. We conclude that the noninvasive localization of interictal HFOs could significantly improve the presurgical evaluation for pediatric patients with epilepsy.

The assessment of oral-motor behavior (OMB) represents one the earliest noninvasive ways to evaluate newborns' well-being and neuromotor behavior. This work aimed at developing a new low-cost, easy-to-use and noninvasive system for a technology-aided assessment of newborns' OMB during bottle feeding. A SUcking MOnitoring Device (SUMOD) was designed and developed to be easily integrated on a typical feeding bottle. A software system was developed to automatically treat and analyze the acquired data: proper algorithms for a fully automatic segmentation and features extraction are proposed and implemented. A set of measures of motor control and coordination are introduced and implemented for the specific application to the OMB analysis. Experimental data were collected on two groups of newborns (healthy versus low birth weight) with the SUMOD in a clinical setting.

In this work a novel unobtrusive technology-aided system is presented and tested for the assessment of newborns' oral-motor behavior and coordination during bottle feeding. A low-cost monitoring device was designed and developed in order to record Suction (S) and Expression (E) pressures from a typical feeding bottle. A software system was developed to automatically treat the data and analyze them. A set of measures of motor control and coordination has been implemented for the specific application to the analysis of sucking behavior. Experimental data were collected with the developed system on two groups of newborns (Healthy vs. Low Birth Weight) in a clinical setting. We identified the most sensitive S features to group differences, and analyzed their correlation with S/E coordination measures. Then, Principal Component Analysis (PCA) was used to explore the system suitability to automatically identify peculiar oral behaviors. Results suggest the suitability of the proposed system to perform an objective technology-aided assessment of the newborn's oral-motor behavior and coordination during the first days of life.

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.

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.