The frontal sharp transient in newborns: An endogenous neurobiomarker concomitant to the physiological and critical transitional period around delivery?

The frontal sharp transient (FST) consists of transient electrical activity recorded around the transitional period from the in to ex utero environment. Although its positive predictive value is assumed, nothing is known about its functionality or origin. The objectives were (i) to define its characteristics and (ii) to develop functional hypothesis. The 128-channels high-resolution electroencephalograms of 20 healthy newborns (37.1-41.6 weeks) were studied. The morphological and time-frequency characteristics of 418 FSTs were analyzed. The source localization of the FSTs was obtained using a finite element head model (5 layers and fontanels) and various source localization methods (distributed and dipolar). The characteristics (duration, slopes, and amplitude) and the localization of FSTs were not modulated by the huge developmental neuronal processes that occur during the very last period of gestation. The sources were located beneath the ventral median part of the frontal lobe around the interhemispheric fissure, suggesting that the olfactory bulbs and orbitofrontal cortex, essential in olfaction and the mother-infant attachment relationship, are likely candidates for the generation of FSTs. FSTs may contribute to the implementation of the functionalities of brain structures involved in the higher-order processing necessary for survival ahead of delivery, with a genetic fingerprint.

The prognostic value of neonatal conventional-EEG monitoring in hypoxic-ischemic encephalopathy during therapeutic hypothermia.

AIM: To determine the prognostic value of conventional electroencephalography (EEG) monitoring in neonatal hypoxic-ischemic encephalopathy (HIE). METHOD: In this multicentre retrospective study, 95 full-term neonates (mean of 39.3wks gestational age [SD  1.4], 36 [38%] females, 59 [62%] males) with HIE (2013-2016) undergoing therapeutic hypothermia were divided between favourable or adverse outcomes. Background EEG activity (French classification scale: 0-1-2-3-4-5) and epileptic seizure burden (epileptic seizure scale: 0-1-2) were graded for seven 6-hour periods. Conventional EEG monitoring was investigated by principal component analysis (PCA), with clustering methods to extract prognostic biomarkers of development at 2 years and infant death. RESULTS: Eighty-one per cent of infants with an adverse outcome had a French classification scale equal to or greater than 3 after H48 (100% at H6-12). The H6-12 epileptic seizure scale was equal to or greater than 1 for 39%, increased to 52% at H30-36 and then remained equal to or greater than 1 for 39% after H48. Forty-five per cent of infants with a favourable outcome had a H6-12 French classification scale equal to or greater than 3, which dropped to 5% after H48; 13% had a H6-12 epileptic seizure scale equal to or greater than 1 but no seizures after H48. Clustering methods based on PCA showed the high efficiency (96%) of conventional EEG monitoring for outcome prediction and allowed the definition of three prognostic EEG biomarkers: H6-78 French classification scale mean, H6-78 French classification scale slope, and H30-78 epileptic seizure scale mean. INTERPRETATION: Early lability and recovery of physiological features is prognostic of a favourable outcome. Seizure onset from the second day should also be considered to accurately predict neurodevelopment in HIE and support the importance of conventional EEG monitoring in HIE in infants cooled with therapeutic hypothermia. WHAT THIS PAPER ADDS: Comprehensive analysis showed the high prognostic efficiency (96%) of conventional electroencephalography (EEG) monitoring. Prognostic EEG biomarkers consist of the grade of background EEG activity, its evolution, and the mean seizure burden. Persistent seizures (H48) without an improvement in background EEG activity were consistently associated with an adverse outcome.

Cortical light scattering during interictal epileptic spikes in frontal lobe epilepsy in children: A fast optical signal and electroencephalographic study.

OBJECTIVE: Interictal epileptic spikes (IES) represent a signature of the transient synchronous and excessive discharge of a large ensemble of cortical heterogeneous neurons. Epilepsy cannot be reduced to a hypersynchronous activation of neurons whose functioning is impaired, resulting on electroencephalogram (EEG) in epileptic seizures or IES. The complex pathophysiological mechanisms require a global approach to the interactions between neural synaptic and nonsynaptic, vascular, and metabolic systems. In the present study, we focused on the interaction between synaptic and nonsynaptic mechanisms through the simultaneous noninvasive multimodal multiscale recording of high-density EEG (HD-EEG; synaptic) and fast optical signal (FOS; nonsynaptic), which evaluate rapid changes in light scattering related to changes in membrane configuration occurring during neuronal activation of IES. METHODS: To evaluate changes in light scattering occurring around IES, three children with frontal IES were simultaneously recorded with HD-EEG and FOS. To evaluate change in synchronization, time-frequency representation analysis of the HD-EEG was performed simultaneously around the IES. To independently evaluate our multimodal method, a control experiment with somatosensory stimuli was designed and applied to five healthy volunteers. RESULTS: Alternating increase-decrease-increase in optical signals occurred 200 ms before to 180 ms after the IES peak. These changes started before any changes in EEG signal. In addition, time-frequency domain EEG analysis revealed alternating decrease-increase-decrease in the EEG spectral power concomitantly with changes in the optical signal during IES. These results suggest a relationship between (de)synchronization and neuronal volume changes in frontal lobe epilepsy during IES. SIGNIFICANCE: These changes in the neuronal environment around IES in frontal lobe epilepsy observed in children, as they have been in rats, raise new questions about the synaptic/nonsynaptic mechanisms that propel the neurons to hypersynchronization, as occurs during IES. We further demonstrate that this noninvasive multiscale multimodal approach is suitable for studying the pathophysiology of the IES in patients.

Phenotype-genotype correlations in 17 new patients with an Xp11.23p11.22 microduplication and review of the literature.

Array comparative genomic hybridization (array CGH) has proven its utility in uncovering cryptic rearrangements in patients with X-linked intellectual disability. In 2009, Giorda et al. identified inherited and de novo recurrent Xp11.23p11.22 microduplications in two males and six females from a wide cohort of patients presenting with syndromic intellectual disability. To date, 14 females and 5 males with an overlapping microduplication have been reported in the literature. To further characterize this emerging syndrome, we collected clinical and microarray data from 17 new patients, 10 females, and 7 males. The Xp11.23p11.2 microduplications detected by array CGH ranged in size from 331 Kb to 8.9 Mb. Five patients harbored 4.5 Mb recurrent duplications mediated by non-allelic homologous recombination between segmental duplications and 12 harbored atypical duplications. The chromosomal rearrangement occurred de novo in eight patients and was inherited in six affected males from three families. Patients shared several common major characteristics including moderate to severe intellectual disability, early onset of puberty, language impairment, and age related epileptic syndromes such as West syndrome and focal epilepsy with activation during sleep evolving in some patients to continuous spikes-and-waves during slow sleep. Atypical microduplications allowed us to identify minimal critical regions that might be responsible for specific clinical findings of the syndrome and to suggest possible candidate genes: FTSJ1 and SHROOM4 for intellectual disability along with PQBP1 and SLC35A2 for epilepsy. Xp11.23p11.22 microduplication is a recently-recognized syndrome associated with intellectual disability, epilepsy, and early onset of puberty in females. In this study, we propose several genes that could contribute to the phenotype.

Negative central activity in extremely preterm newborns: EEG characterization and relationship with brain injuries and neurodevelopmental outcome.

OBJECTIVE: To characterize Negative Central Activity (NCA), an overlooked electroencephalographic activity of preterm newborns and investigate its relationship with brain injuries, dysfunction, and neurodevelopmental outcome. METHODS: 109 preterm infants (23-28 weeks) were retrospectively included. NCA were selected at the negative peak on EEG. Individual averaged NCA were automatically characterized. Brain structural data were collected from cranial ultrasounds (cUS). The neurodevelopmental outcome at two years of age was assessed by the Denver Developmental Screening Test-II. RESULTS: Thirty-six (33%) children showed NCA: 6,721 NCA were selected, a median of 75 (interquartile range, 25/157.3) per EEG. NCA showed a triphasic morphology, with a mean amplitude and duration of the negative component of 24.6-40.0 µV and 222.7-257.3 ms. The presence of NCA on EEG was associated with higher intraventricular haemorrhage (IVH) grade on the first (P = 0.016) and worst neonatal cUS (P < 0.001) and poorer neurodevelopmental outcome (P < 0.001). CONCLUSIONS: NCA is an abnormal EEG feature of extremely preterm newborns that may correspond to the functional neural impact of a vascular pathology. SIGNIFICANCE: The NCA relationships with an adverse outcome and the presence/severity of IVH argue for considering NCA in the assessment of pathological processes in the developing brain network and for early outcome prediction.

Predicting the Neurodevelopmental Outcome in Extremely Preterm Newborns Using a Multimodal Prognostic Model Including Brain Function Information.

Importance: Early assessment of the prognosis of preterm newborns is crucial for accurately informing parents and making treatment decisions. The currently available prognostic models rarely incorporate functional brain information from conventional electroencephalography (cEEG). Objective: To examine the performance of a multimodal model combining (1) brain function information with (2) brain structure information (cranial ultrasonography), and (3) perinatal and (4) postnatal risk factors for the prediction of death or neurodevelopmental impairment (NDI) in extremely preterm infants. Design, Setting, and Participants: Preterm newborns (23-28 weeks' gestational age) admitted to the neonatal intensive care unit at Amiens-Picardie University Hospital were retrospectively included (January 1, 2013, to January 1, 2018). Risk factors from the 4 categories were collected during the first 2 weeks post delivery. Neurodevelopmental impairment was assessed at age 2 years with the Denver Developmental Screening Test II. No or moderate NDI was considered a favorable outcome. Death or severe NDI was considered an adverse outcome. Data analysis was performed from August 26, 2021, to March 31, 2022. Main Outcomes and Measures: After the selection of variables significantly associated with outcome, 4 unimodal prognostic models (considering each category of variable independently) and 1 multimodal model (considering all variables simultaneously) were developed. After a multivariate analysis for models built with several variables, decision-tree algorithms were run on each model. The areas under the curve for decision-tree classifications of adverse vs favorable outcomes were determined for each model, compared using bootstrap tests, and corrected for type I errors. Results: A total of 109 newborns (58 [53.2% male]) born at a mean (SD) gestational age of 26.3 (1.1) weeks were included. Among them, 52 (47.7%) had a favorable outcome at age 2 years. The multimodal model area under the curve (91.7%; 95% CI, 86.4%-97.0%) was significantly higher than those of the unimodal models (P < .003): perinatal model (80.6%; 95% CI, 72.5%-88.7%), postnatal model (81.0%; 95% CI, 72.6%-89.4%), brain structure model (cranial ultrasonography) (76.6%; 95% CI, 67.8%-85.3%), and brain function model (cEEG) (78.8%; 95% CI, 69.9%-87.7%). Conclusions and Relevance: In this prognostic study of preterm newborns, the inclusion of brain information in a multimodal model was associated with significant improvement in the outcome prediction, which may have resulted from the complementarity of the risk factors and reflected the complexity of the mechanisms that interfered with brain maturation and led to death or NDI.

Use of EEG in neonatal hypoxic-ischemic encephalopathy: A French survey of current practice and perspective for improving health care.

OBJECTIVES: Controlled therapeutic hypothermia (CTH) is a standard of care in the management of neonatal hypoxic-ischemic encephalopathy HIE in newborns after 36 weeks of gestational age (WGA) in France. The electroencephalogram (EEG) plays a major role in HIE diagnosis and follow-up. We conducted a French national survey on the current use of EEG in newborn undergoing CTH. METHODS: Between July and October 2021, an email survey was sent to the heads of the Neonatal intensive care units (NICUs) in metropolitan and overseas French departments and territories. RESULTS: Out of 67, 56 (83%) of NICUs responded. All of them performed CTH in children born after 36 WGA with clinical and biological criteria of moderate to severe HIE. 82% of the NICUs used conventional EEG (cEEG) before 6 h of life (H6), prior to CTH being performed, to inform decisions about its use. However, half of the 56 NICUs had limited access after regular working hours. 51 of the 56 centers (91%) used cEEG, either short-lasting or continuous monitoring during cooling, while 5 centers conducted only amplitude EEG (aEEG). Only 4 of 56 centers (7%) used cEEG systematically both prior to CTH and for continuous monitoring under CTH. DISCUSSION: The use of cEEG in the management of neonatal HIE was widespread in NICUs, but with significant disparities when considering 24-hour access. The introduction of a centralized neurophysiological on-call system grouping several NICUs would be of major interest for most centers which do not have the facility of EEG outside working hours.

A transposase-derived gene required for human brain development.

DNA transposable elements and transposase-derived genes are present in most living organisms, including vertebrates, but their function is largely unknown. PiggyBac Transposable Element Derived 5 (PGBD5) is an evolutionarily conserved vertebrate DNA transposase-derived gene with retained nuclease activity in cells. Vertebrate brain development is known to be associated with prominent neuronal cell death and DNA breaks, but their causes and functions are not well understood. Here, we show that PGBD5 contributes to normal brain development in mice and humans, where its deficiency causes disorder of intellectual disability, movement and seizures. In mice, Pgbd5 is required for the developmental induction of post-mitotic DNA breaks and recurrent somatic genome rearrangements in neurons. Together, these studies nominate PGBD5 as the long-hypothesized neuronal DNA nuclease required for brain function in mammals.

Continuous monitoring of neonatal cortical activity: A major step forward.

Montazeri Moghadam et al.1 report an automated algorithm to visually convert EEG recordings to real-time quantified interpretations of EEG in neonates. The resulting measure of the brain state of the newborn (BSN) bridges several gaps in neurocritical care monitoring.

Behavioral-state development and sleep-state differentiation during early ontogenesis.

Sleep is a key process in neurodevelopment and essential for the maturation of fundamental brain functions. Premature birth can disturb the initial steps of sleep maturation, which may contribute to the impairment of neurodevelopment. It is thus fundamental to understand the maturation of the various sleep states and the quality of cerebral function in each vigilance state, as well as the development of sleep cyclicity, in at-risk neonatal infants, particularly those born premature. The objective of this review is to provide a precise description of sleep states and cycles and their rhythmic organization in premature and term newborns according to their gestational age. Technical aspects of polysomnography, which requires a high level of expertise in neonates, are also described. Principles of the visual interpretation of polysomnography, including the simultaneous analysis of behavioral (spontaneous motricity and eye movements), polysomnographic parameters (electro-oculogram, electrocardiogram, respiration), and electroencephalography patterns are presented. The neurophysiology of sleep ontogenesis and its interaction with brain maturation are discussed, highlighting the crucial role of sleep states and their duration in premature newborns. In particular, the involvement of myoclonic twitches in functional connectivity in sensorimotor development is discussed. Indeed, sleep quality, determined by combined polysomnographic parameters, reflects either normal or pathological developmental processes during the neonatal period. The fundamental place of neurophysiological explorations in the early detection of sleep disorders is discussed, as well as their potential consequences on neurodevelopmental care to improve the prevention of neurodevelopmental impairment.

Technical recommendations and interpretation guidelines for electroencephalography for premature and full-term newborns.

Electroencephalography (EEG) of neonatal patients is amongst the most valuable diagnostic and prognostic tool. EEG recordings, acquired at the bedside of infants, evaluate brain function and the maturation of premature and extremely premature infants. Strict conditions of acquisition and interpretation must be respected to guarantee the quality of the EEG and ensure its safety for fragile children. This article provides guidance for EEG acquisition including: (1) the required equipment and devices, (2) the modalities of installation and asepsis precautions, and (3) the digital signal acquisition parameters to use during the recording. The fundamental role of a well-trained technician in supervising the EEG recording is emphasized. In parallel to the acquisition recommendations, we present a guideline for EEG interpretation and reporting. The successive steps of EEG interpretation, from reading the EEG to writing the report, are described. The complexity of the EEG signal in neonates makes artefact detection difficult. Thus, we provide an overview of certain characteristic artefacts and detail the methods for eliminating them.

Back to basics: the neuronal substrates and mechanisms that underlie the electroencephalogram in premature neonates.

Electroencephalography is the only clinically available technique that can address the premature neonate normal and pathological functional development week after week. The changes in the electroencephalogram (EEG) result from gradual structural and functional modifications that arise during the last trimester of pregnancy. Here, we review the structural changes over time that underlie the establishment of functional immature neural networks, the impact of certain anatomical specificities (fontanelles, connectivity, etc.) on the EEG, limitations in EEG interpretation, and the utility of high-resolution EEG (HR-EEG) in premature newborns (a promising technique with a high degree of spatiotemporal resolution). In particular, we classify EEG features according to whether they are manifestations of endogenous generators (i.e. theta activities that coalesce with a slow wave or delta brushes) or come from a broader network. Furthermore, we review publications on EEG in premature animals because the data provide a better understanding of what is happening in premature newborns. We then discuss the results and limitations of functional connectivity analyses in premature newborns. Lastly, we report on the magnetoelectroencephalographic studies of brain activity in the fetus. A better understanding of complex interactions at various structural and functional levels during normal neurodevelopment (as assessed using electroencephalography as a benchmark method) might lead to better clinical care and monitoring for premature neonates.

Normal EEG during the neonatal period: maturational aspects from premature to full-term newborns.

Electroencephalography (EEG) is the reference tool for the analysis of brain function, reflecting normal and pathological neuronal network activity. During the neonatal period, EEG patterns evolve weekly, according to gestational age. The first analytical criteria for the various maturational stages and standardized neonatal EEG terminology were published by a group of French neurophysiologists training in Paris (France) in 1999. These criteria, defined from analog EEG, were completed in 2010 with digital EEG analysis. Since then, this work has continued, aided by the technical progress in EEG acquisition, the improvement of knowledge on the maturating processes of neuronal networks, and the evolution of critical care. In this review, we present an exhaustive and didactic overview of EEG characteristics from extremely premature to full-term infants. This update is based on the scientific literature, enhanced by the study of normal EEGs of extremely premature infants by our group of neurophysiologists. For educational purposes, particular attention has been paid to illustrations using new digital tools.

Impact of prematurity on neurodevelopment.

The consequences of prematurity on brain functional development are numerous and diverse, and impact all brain functions at different levels. Prematurity occurs between 22 and 36 weeks of gestation. This period is marked by extreme dynamics in the physiologic maturation, structural, and functional processes. These different processes appear sequentially or simultaneously. They are dependent on genetic and/or environmental factors. Disturbance of these processes or of the fine-tuning between them, when caring for premature children, is likely to induce disturbances in the structural and functional development of the immature neural networks. These will appear as impairments in learning skills progress and are likely to have a lasting impact on the development of children born prematurely. The level of severity depends on the initial alteration, whether structural or functional. In this chapter, after having briefly reviewed the neurodevelopmental, structural, and functional processes, we describe, in a nonexhaustive manner, the impact of prematurity on the different brain, motor, sensory, and cognitive functions.

Temporal and Spatial Dynamics of Different Interictal Epileptic Discharges: A Time-Frequency EEG Approach in Pediatric Focal Refractory Epilepsy.

Objective: Characterization of the spatial and temporal dynamics of interictal epileptic discharges (IED) using time-frequency analysis (TFA) and electrical-source localization (ESL). Methods: TFA was performed on IED (spikes, spike waves, and polyspike waves) recorded by high-density-EEG (HD-EEG) in 19 refractory focal epileptic children. Temporal modulations related to IEDs were analyzed in a time window around the IED peaks [-1,000 to 1,000 ms]. Spatial modulations were analyzed by ESL in the time-frequency and time domains. Results: IED were associated with complex power spectral modulations. We observed increases in power spectrum (IPS) patterns specific to IED type. For spikes, the TFA pattern consisted of an IPS (-100 to +100 ms, 4-50 Hz). For spike waves, the IPS was followed by a second IPS (+100 to +400 ms, 4-10 Hz), corresponding to the slow wave. IPS patterns were preceded (-400 to -100 ms, 4-40 Hz), and followed (+100 to +400 ms) by a decrease in the power spectrum (DPS) (n = 8). For 14 out of 19 patients, at least one ESL method was concordant with the epileptogenic area. For the remaining five patients, all of them had temporal epilepsies. ESL in the time-frequency domain (DPS/IPS) provided concordant (n = 6) or complementary (n = 4) information to the ESL in the time domain concerning the epileptogenic zone. ESL in time-frequency domain (DPS/IPS) was the only method to provide concordant information concerning the epileptogenic zone in three patients. Significance: TFA demonstrates complex time-frequency modulations of the neuronal networks around IED, suggesting that the pathological mechanisms are initiated well before onset of the classical hyper-synchronization of the IED. Combining time and time-frequency analysis of the ESL provides complementary information to define the epileptogenic zone in refractory focal epilepsy.

Stretch syncope or epileptic seizure? A pathologic hypothesis for self-induced stretch syncope.

We report on a 7-year-old female who presented paroxysmal episodes of loss of consciousness with clonic movements. The electroencephalogram (EEG) evidenced diffuse slow wave activations, with no symptoms. Epilepsy was suspected but antiepileptic drugs were ineffective. Video-EEG monitoring revealed that the syncope was triggered by stretching with a tachycardia that started during the stretch maneuver and diffuse slow waves on the EEG 2s before the symptoms. Stretch syncope can result in striking manifestations with subcortically driven clonic movements that can be mistaken for signs of epilepsy. Stretching might lead to transient hypoxia of the brainstem; in turn, this might activate the thalamocortical loop and thus generate cardiovascular changes, EEG slow waves, and physical manifestations.

Functional and Structural Network Disorganizations in Typical Epilepsy With Centro-Temporal Spikes and Impact on Cognitive Neurodevelopment.

Epilepsy with Centrotemporal Spikes (ECTS) is the most common form of self-limited focal epilepsy. The pathophysiological mechanisms by which ECTS induces neuropsychological impairment in 15-30% of affected children remain unclear. The objective of this study is to review the current state of knowledge concerning the brain structural and functional changes that may be involved in cognitive dysfunctions in ECTS. Structural brain imaging suggests the presence of subtle neurodevelopmental changes over the epileptogenic zone and over distant regions in ECTS. This structural remodeling likely occurs prior to the diagnosis and evolves over time, especially in patients with cognitive impairment, suggesting that the epileptogenic processes might interfere with the dynamics of the brain development and/or the normal maturation processes. Functional brain imaging demonstrates profound disorganization accentuated by interictal epileptic spikes (IES) in the epileptogenic zone and in remote networks in ECTS. Over the epileptogenic zone, the literature demonstrates changes in term of neuronal activity and synchronization, which are effective several hundred milliseconds before the IES. In the same time window, functional changes are also observed in bilateral distant networks, notably in the frontal and temporal lobes. Effective connectivity demonstrates that the epileptogenic zone constitutes the key area at the origin of IES propagation toward distant cortical regions, including frontal areas. Altogether, structural and functional network disorganizations, in terms of: (i) power spectral values, (ii) functional and effective connectivity, are likely to participate in the cognitive impairment commonly reported in children with ECTS. These results suggest a central and causal role of network disorganizations related to IES in the neuropsychological impairment described in ECTS children.

Identifying neural drivers of benign childhood epilepsy with centrotemporal spikes.

Epilepsy is a neurological disorder characterized by abnormal electrical discharges in a group of brain cells. Benign childhood epilepsy, which affect children under the age of 12 years, has been reported to contribute to the cognitive impairment of these children, even in the absence of structural abnormalities. Functional connectivity models have been applied to provide a deeper understanding of the processes that control and regulate interictal activity of benign childhood epilepsy. These studies have shown regions of increased connectivity and activity, particularly at the epileptic zone, which is usually the central region around the sensorimotor cortex, and in the immediate regions surrounding the zone and reduced activity in distant regions, such as the frontal lobe and temporal regions. The present study was designed to identify the neural drivers involved in the initiation and propagation of epileptic activity and the causal relationships between brain regions with increased and decreased connectivity and functional activity. We used three different models to identify neural drivers and casual connectivity with dynamic causal modelling (DCM) of EEG data. All models showed that the central region, the source of the epileptic activity, is the major driver of the brain network during interictal discharges. Other regions include the temporoparietal junction and temporal pole. The central region also had influence on the frontal and contralateral hemisphere, which might explain the cognitive deficits observed in these patients.

Local and Distant Dysregulation of Synchronization Around Interictal Spikes in BECTS.

Objective: High Density electroencephalography (HD EEG) is the reference non-invasive technique to investigate the dynamics of neuronal networks in Benign Epilepsy with Centro-Temporal Spikes (BECTS). Analysis of local dynamic changes surrounding Interictal Epileptic Spikes (IES) might improve our knowledge of the mechanisms that propel neurons to the hypersynchronization of IES in BECTS. Transient distant changes in the dynamics of neurons populations may also interact with neuronal networks involved in various functions that are impaired in BECTS patients. Methods: HD EEG (64 electrodes) of eight well-characterized BECTS patients (8 males; mean age: 7.2 years, range: 5-9 years) were analyzed. Unilateral IES were selected in 6 patients. They were bilateral and independent in 2 other patients. This resulted in a total of 10 groups of IES. Time-frequency analysis was performed on HD EEG epochs around the peak of the IES (±1000 ms), including phase-locked and non-phase-locked activities to the IES. The time frequency analyses were calculated for the frequencies between 4 and 200 Hz. Results: Time-frequency analysis revealed two patterns of dysregulation of the synchronization between neuronal networks preceding and following hypersynchronization of interictal spikes (±400 ms) in the epileptogenic zone. Dysregulation consists of either desynchronization (n = 6) or oscillating synchronization (n = 4) (4-50 Hz) surrounding the IES. The 2 patients with bilateral IES exhibited only local desynchronization whatever the IES considered. Distant desynchronization in low frequencies within the same window occurs simultaneously in bilateral frontal, temporal and occipital areas (n = 7). Significance: Using time-frequency analysis of HD EEG data in a well-defined population of BECTS, we demonstrated repeated complex changes in the dynamics of neuronal networks not only during, but also, before and after the IES. In the epileptogenic zone, our results found more complex reorganization of the local network than initially thought. In line with previous results obtained at a microscopic or macroscopic level, these changes suggested the variability strategies of neuronal assemblies to raise IES. Distant changes from the epileptogenic zone in desynchronization observed in the same time window suggested interactions between larger embedded networks and opened new avenues about their possible role in the underlying mechanism leading to cognitive deficits.

Non-invasive, multimodal analysis of cortical activity, blood volume and neurovascular coupling in infantile spasms using EEG-fNIRS monitoring.

Although infantile spasms can be caused by a variety of etiologies, the clinical features are stereotypical. The neuronal and vascular mechanisms that contribute to the emergence of infantile spasms are not well understood. We performed a multimodal study by simultaneously recording electroencephalogram and functional Near-infrared spectroscopy in an intentionally heterogeneous population of six children with spasms in clusters. Regardless of the etiology, spasms were accompanied by two phases of hemodynamic changes; an initial change in the cerebral blood volume (simultaneously with each spasm) followed by a neurovascular coupling in all children except for the one with a large porencephalic cyst. Changes in cerebral blood volume, like the neurovascular coupling, occurred over frontal areas in all patients regardless of any brain damage suggesting a diffuse hemodynamic cortical response. The simultaneous motor activation and changes in cerebral blood volume might result from the involvement of the brainstem. The inconstant neurovascular coupling phase suggests a diffuse activation of the brain likely resulting too from the brainstem involvement that might trigger diffuse changes in cortical excitability.