Functional connectivity between medial pulvinar and cortical networks as a predictor of arousal to noxious stimuli during sleep.

The interruption of sleep by a nociceptive stimulus is favoured by an increase in the pre-stimulus functional connectivity between sensory and higher level cortical areas. In addition, stimuli inducing arousal also trigger a widespread electroencephalographic (EEG) response reflecting the coordinated activation of a large cortical network. Because functional connectivity between distant cortical areas is thought to be underpinned by trans-thalamic connections involving associative thalamic nuclei, we investigated the possible involvement of one principal associative thalamic nucleus, the medial pulvinar (PuM), in the sleeper's responsiveness to nociceptive stimuli. Intra-cortical and intra-thalamic signals were analysed in 440 intracranial electroencephalographic (iEEG) segments during nocturnal sleep in eight epileptic patients receiving laser nociceptive stimuli. The spectral coherence between the PuM and 10 cortical regions grouped in networks was computed during 5 s before and 1 s after the nociceptive stimulus and contrasted according to the presence or absence of an arousal EEG response. Pre- and post-stimulus phase coherence between the PuM and all cortical networks was significantly increased in instances of arousal, both during N2 and paradoxical (rapid eye movement [REM]) sleep. Thalamo-cortical enhancement in coherence involved both sensory and higher level cortical networks and predominated in the pre-stimulus period. The association between pre-stimulus widespread increase in thalamo-cortical coherence and subsequent arousal suggests that the probability of sleep interruption by a noxious stimulus increases when it occurs during phases of enhanced trans-thalamic transfer of information between cortical areas.

Amygdala and anterior insula control the passage from nociception to pain.

Activation of the spinothalamic system does not always result in a subjective pain perception. While the cerebral network processing nociception is relatively well known, the one underlying its transition to conscious pain remains poorly described. We used intracranial electroencephalography in epileptic patients to investigate whether the amplitudes and functional connectivity of posterior and anterior insulae (PI and AI) and amygdala differ according to the subjective reports to laser stimuli delivered at a constant intensity set at nociceptive threshold. Despite the constant intensity of stimuli, all patients reported variable subjective perceptions from one stimulus to the other. Responses in the sensory PI remained stable throughout the experiment, hence reflecting accurately the stability of the stimulus. In contrast, both AI and amygdala responses showed significant enhancements associated with painful relative to nonpainful reports, in a time window corresponding to the conscious integration of the stimulus. Functional connectivity in the gamma band between these two regions increased significantly, both before and after stimuli perceived as painful. While the PI appears to transmit faithfully the actual stimulus intensity received via the spinothalamic tract, the AI and the amygdala appear to play a major role in the transformation of nociceptive signals into a painful perception.

Intracortical Functional Connectivity Predicts Arousal to Noxious Stimuli during Sleep in Humans.

Nociceptive stimuli disrupt sleep, but may, or may not, entail an arousal. While arousal reactions go along with the activation of a widespread cortical network, the factors enabling such activation remain unknown. Here we used intracranial EEG in humans to test the relation between the cortical activity immediately preceding a noxious stimulus and the capacity of such a stimulus to trigger arousal. Intracranial EEG signals were analyzed during all-night sleep in 14 epileptic patients (4 women), who received laser stimuli slightly above their individual pain threshold. During 5 s preceding each stimulus, the functional correlation (spectral phase-coherence) between the main spinothalamic sensory area (posterior insula) and 12 other brain regions, grouped in four networks, as well as their spectral contents, were contrasted according to the presence of a stimulus-induced arousal, and then fed into a logistic regression model to assess their predictive value. Enhanced prestimulus phase-coherence between the sensory posterior insula and neocortical and limbic areas increased significantly the probability of arousal to nociceptive stimuli, in both slow-wave (N2) and rapid eye movements/paradoxical sleep. Furthermore, during N2 sleep, arousal was facilitated by stimulus delivery in periods of attenuated slow-wave activity. Together, these data indicate that sleep micro-states with enhanced interareal communication facilitate information transfer from sensory to higher-order cortical areas, and hence physiological arousal.SIGNIFICANCE STATEMENT Sleep is commonly subdivided into stages based on specific electrophysiological characteristics; however, within each single sleep stage, the functional state of the brain is continuously changing. Here we show that the probability for a phasic noxious stimulus to entail an arousal is modulated by the prestimulus interareal phase-coherence between sensory and higher-level cortical areas. Fluctuations in interareal communication immediately before the noxious stimulus may determine the responsiveness to incoming input by facilitating or preventing the transfer of noxious information from sensory to multiple higher-level cortical networks.

Long-term satisfaction after extraoperative invasive EEG recording.

This retrospective cohort study investigated 53 patients with drug-resistant focal epilepsy and identified factors predictive of long-term satisfaction of patients and families following extraoperative intracranial EEG (iEEG) recording. The mixed model analysis assessed the utility of intracranial EEG (iEEG) predictor variables, including the seizure-onset zone (SOZ), modulation index (MI), and naming-related high-gamma activity. Modulation index, quantifying the coupling between high-frequency activity at >80 Hz and local slow wave at 3-4 Hz, effectively functions as a surrogate marker of the burden of interictal spike-and-slow-wave discharges. The mixed model specifically incorporated 'subtraction-MI', defined as the subtraction of mean z-score normalized MI across all preserved sites from that across all resected sites. Auditory naming-related high-gamma activity at 70-110 Hz is a biomarker to characterize the underlying language and speech function. The model incorporated 'maximum resected high-gamma', defined as the high-gamma percent change largest among sites included in the resected language-dominant hemispheric region. The model also incorporated the clinical and imaging profiles of given patients. The analysis revealed that complete removal of SOZ (p = 0.003) and younger patient age (p = 0.040) were independently associated with greater satisfaction. Neither 'subtraction-MI' nor 'maximum naming-related high-gamma' showed a significant and independent association with long-term satisfaction in our patient cohort. The observed impact of complete resection of SOZ and early surgery can be considered when counseling candidates for epilepsy surgery.

Local sleep spindles in the human thalamus.

KEY POINTS: Sleep spindles have recently been shown to occur not only across multiple neocortical regions but also locally in restricted cortical areas. Here we show that local spindles are indeed present in the human posterior thalamus. Thalamic local spindles had lower spectral power than non-local ones. While non-local thalamic spindles had equal local and non-local cortical counterparts, local thalamic spindles had significantly more local cortical counterparts (i.e. occurring in a single cortical site). The preferential association of local thalamic and cortical spindles supports the notion of thalamocortical loops functioning in a modular way. ABSTRACT: Sleep spindles are believed to subserve many sleep-related functions, from memory consolidation to cortical development. Recent data using intracerebral recordings in humans have shown that they occur across multiple neocortical regions but may also be spatially restricted to specific brain areas (local spindles). The aim of this study was to characterize spindles at the level of the human posterior thalamus, with the hypothesis that, besides the global thalamic spindling activity usually observed, local spindles could also be present in the thalamus. Using intracranial, time-frequency EEG recordings in 17 epileptic patients, we assessed the distribution of thalamic spindles during natural sleep stages N2 and N3 in six thalamic nuclei. Local spindles (i.e. spindles present in a single pair of recording contacts) were observed in all the thalamic regions explored, and compared with non-local spindles in terms of intrinsic properties and cortical counterparts. Thalamic local and non-local spindles did not differ in density, frequency or duration, but local spindles had lower spectral power than non-local ones. Each thalamic spindle had a cortical counterpart. While non-local thalamic spindles had equal cortical local and non-local counterparts, local thalamic spindles had significantly more local cortical counterparts (i.e. occurring in a single cortical site). The preferential association of local thalamic and cortical spindles supports the notion of thalamocortical loops functioning in a modular way.

A Novel Focal Seizure Pattern Generated in Superficial Layers of the Olfactory Cortex.

Seizure patterns identified in focal epilepsies caused by diverse etiologies are likely due to different pathogenic mechanisms. We describe here a novel, region-specific focal seizure pattern that mimics seizure activity observed in a subpopulation of patients submitted to presurgical monitoring with intracerebral electrodes. Distinctive seizure-like events (SLEs) are induced in the olfactory regions by acute treatment of both tangential brain slices and the isolated guinea pig brain with the potassium channel blocker 4-aminopyridine. Analysis of field potentials, intracellular activities, and extracellular potassium changes demonstrates that SLEs in the piriform cortex initiate in the superficial layer 1 lacking principal neurons with an activity-dependent increase of extracellular potassium. SLE progression (but not onset) does not require the participation of synaptic transmission and is mediated by diffusion of potassium to deep cortical layers. The novel seizure pattern here described is not observed in other cortical regions; it is proposed to rely on the peculiar organization of the superficial piriform cortex layers, which are characterized by unmyelinated axons and perisynaptic astroglial envelopes. This study reveals a sequence of ictogenic events in the olfactory cortex that were never described before in other cortical structures and supports the notion that altered potassium homeostasis and unmyelinated fibers may represent a potential vehicle for focal ictogenesis.SIGNIFICANCE STATEMENT We describe a novel seizure pattern peculiar of the olfactory cortex that resembles focal seizures with low-voltage fast activity at onset observed in humans. The findings suggest that network mechanisms responsible for seizure onset can be region specific.

Intracerebral electroencephalography in targeting anterior thalamic nucleus for deep brain stimulation in refractory epilepsy.

BACKGROUND: Results of DBS of ATN in refractory epilepsy depend on accuracy of the electrode's location. We searched for characteristic intraoperative, intracerebral EEG recording pattern from anterior thalamic nuclei (ATNs) as a biological marker for verifying the electrode's position. METHODS: There were six patients with refractory epilepsy scheduled for deep brain stimulation (DBS) procedure. At surgery, to map the target, we recorded EEG from each lead of DBS electrodes. One patient underwent a 24 hours EEG with continuous recording from both ATNs before internalization of stimulator units. RESULTS: In all patients we recorded spontaneous bioelectric activity of ATNs. The pattern of the recording from the ATN was similar in all cases. In the one patient where 24-hour recording was done with simultaneous scalp EEG, a complex partial seizure was captured. CONCLUSION: This is the first report of using DBS electrode for intraoperative EEG recordings from the ATN in patients with refractory epilepsy. Since we managed to find the characteristic pattern of bioelectric activity of ATN, this technique seems to be a promising method for targeting this structure during the operation.

The hemodynamic response to interictal epileptic discharges localizes the seizure-onset zone.

OBJECTIVE: Intracranial electroencephalography (EEG), performed presurgically in patients with drug-resistant and difficult-to-localize focal epilepsy, samples only a small fraction of brain tissue and thus requires strong hypotheses regarding the possible localization of the epileptogenic zone. EEG/fMRI (functional magnetic resonance imaging), a noninvasive tool resulting in hemodynamic responses, could contribute to the generation of these hypotheses. This study assessed how these responses, despite their interictal origin, predict the seizure-onset zone (SOZ). METHODS: We retrospectively studied 37 consecutive patients who underwent stereo-EEG (SEEG) and EEG/fMRI that resulted in significant hemodynamic responses. Hemodynamic response maps were co-registered to postimplantation anatomic imaging, allowing inspection of these responses in relation to SEEG electrode's location. The area containing the most significant t-value (primary cluster) explored with an electrode was assessed for concordance with SEEG-defined SOZ. Discriminant analysis was performed to distinguish the primary clusters having a high probability of localizing the SOZ. RESULTS: Thirty-one patients had at least one study with primary cluster explored with an electrode, and 24 (77%) had at least one study with primary cluster concordant with the SOZ. Each patient could have multiple types of interictal discharge and therefore multiple studies. Among 59 studies from the 37 patients, 44 had a primary cluster explored with an electrode and 30 (68%) were concordant with the SOZ. Discriminant analysis showed that the SOZ is predictable with high confidence (>90%) if the primary cluster is highly significant and if the next significant cluster is much less significant or absent. SIGNIFICANCE: The most significant hemodynamic response to interictal discharges delineates the subset of the irritative zone that generates seizures in a high proportion of patients with difficult-to-localize focal epilepsy. EEG/fMRI generates responses that are valuable targets for electrode implantation and may reduce the need for implantation in patients in whom the most significant response satisfies the condition of our discriminant analysis.

Thalamic Responses to Nociceptive-Specific Input in Humans: Functional Dichotomies and Thalamo-Cortical Connectivity.

While nociceptive cortical activation is now well characterized in humans, understanding of the nociceptive thalamus remains largely fragmentary. We used laser stimuli and intracerebral electrodes in 17 human subjects to record nociceptive-specific field responses in 4 human thalamic nuclei and a number of cortical areas. Three nuclei known to receive spinothalamic (STT) projections in primates (ventro-postero-lateral [VPL], anterior pulvinar [PuA], and central lateral [CL]) exhibited responses with similar latency, indicating their parallel activation by nociceptive afferents. Phase coherence analysis, however, revealed major differences in their functional connectivity: while VPL and PuA drove a limited set of cortical targets, CL activities were synchronized with a large network including temporal, parietal, and frontal areas. Our data suggest that STT afferents reach simultaneously a set of lateral and medial thalamic regions unconstrained by traditional nuclear borders. The broad pattern of associated cortical networks suggests that a single nociceptive volley is able to trigger the sensory, cognitive, and emotional activities that underlie the complex pain experience. The medial pulvinar, an associative nucleus devoid of STT input, exhibited delayed responses suggesting its dependence on descending cortico-thalamic projections. Its widespread cortical connectivity suggests a role in synchronizing parietal, temporal, and frontal activities, hence contributing to the access of noxious input to conscious awareness.

Pain networks from the inside: Spatiotemporal analysis of brain responses leading from nociception to conscious perception.

Conscious perception of painful stimuli needs the contribution of an extensive cortico-subcortical network, and is completed in less than one second. While initial activities in operculo-insular and mid-cingulate cortices have been extensively assessed, the activation timing of most areas supporting conscious pain has barely been studied. Here we used intracranial EEG to investigate the dynamics of 16 brain regions (insular, parietal, prefrontal, cingulate, hippocampal and limbic) during the first second following nociceptive-specific laser pulses. Three waves of activation could be defined according to their temporal relation with conscious perception, ascertained by voluntary motor responses. Pre-conscious activities were recorded in the posterior insula, operculum, mid-cingulate and amygdala. Antero-insular, prefrontal and posterior parietal activities started later and developed during time-frames consistent with conscious voluntary reactions. Responses from hippocampus, perigenual and perisplenial cingulate developed latest and persisted well after conscious perception occurred. Nociceptive inputs reach simultaneously sensory and limbic networks, probably through parallel spino-thalamic and spino-parabrachial pathways, and the initial limbic activation precedes conscious perception of pain. Access of sensory information to consciousness develops concomitant to fronto-parietal activity, while late-occurring responses in the hippocampal region, perigenual and posterior cingulate cortices likely underlie processes linked to memory encoding, self-awareness and pain modulation. Hum Brain Mapp 37:4301-4315, 2016. © 2016 Wiley Periodicals, Inc.

EEG desynchronization during phasic REM sleep suppresses interictal epileptic activity in humans.

OBJECTIVE: Rapid eye movement (REM) sleep has a suppressing effect on epileptic activity. This effect might be directly related to neuronal desynchronization mediated by cholinergic neurotransmission. We investigated whether interictal epileptiform discharges (IEDs) and high frequency oscillations-a biomarker of the epileptogenic zone-are evenly distributed across phasic and tonic REM sleep. We hypothesized that IEDs are more suppressed during phasic REM sleep because of additional cholinergic drive. METHODS: Twelve patients underwent polysomnography during long-term combined scalp-intracerebral electroencephalography (EEG) recording. After sleep staging in the scalp EEG, we identified segments of REM sleep with rapid eye movements (phasic REM) and segments of REM sleep without rapid eye movements (tonic REM). In the intracerebral EEG, we computed the power in frequencies <30 Hz and from 30 to 500 Hz, and marked IEDs, ripples (>80 Hz) and fast ripples (>250 Hz). We grouped the intracerebral channels into channels in the seizure-onset zone (SOZ), the exclusively irritative zone (EIZ), and the normal zone (NoZ). RESULTS: Power in frequencies <30 Hz was lower during phasic than tonic REM sleep (p < 0.001), most likely reflecting increased desynchronization. IEDs, ripples and fast ripples, were less frequent during phasic than tonic REM sleep (phasic REM sleep: 39% of spikes, 35% of ripples, 18% of fast ripples, tonic REM sleep: 61% of spikes, 65% of ripples, 82% of fast ripples; p < 0.001). In contrast to ripples in the epileptogenic zone, physiologic ripples were more abundant during phasic REM sleep (phasic REM sleep: 73% in NoZ, 30% in EIZ, 28% in SOZ, tonic REM sleep: 27% in NoZ, 70% in EIZ, 72% in SOZ; p < 0.001). SIGNIFICANCE: Phasic REM sleep has an enhanced suppressive effect on IEDs, corroborating the role of EEG desynchronization in the suppression of interictal epileptic activity. In contrast, physiologic ripples were increased during phasic REM sleep, possibly reflecting REM-related memory consolidation and dreaming.

Comparison of Brain Networks During Interictal Oscillations and Spikes on Magnetoencephalography and Intracerebral EEG.

Electromagnetic source localization in electroencephalography (EEG) and magnetoencephalography (MEG) allows finding the generators of transient interictal epileptiform discharges ('interictal spikes'). In intracerebral EEG (iEEG), oscillatory activity (above 30 Hz) has also been shown to be a marker of neuronal dysfunction. Still, the difference between networks involved in transient and oscillatory activities remains largely unknown. Our goal was thus to extract and compare the networks involved in interictal oscillations and spikes, and to compare the non-invasive results to those obtained directly within the brain. In five patients with both MEG and iEEG recordings, we computed correlation graphs across regions, for (1) interictal spikes and (2) epileptic oscillations around 30 Hz. We show that the corresponding networks can involve a widespread set of regions (average of 10 per patient), with only partial overlap (38 % of the total number of regions in MEG, 50 % in iEEG). The non-invasive results were concordant with intracerebral recordings (79 % for the spikes and 50 % for the oscillations). We compared our interictal results to iEEG ictal data. The regions labeled as seizure onset zone (SOZ) belonged to interictal networks in a large proportion of cases: 75 % (resp. 58 %) for spikes and 58 % (resp. 33 %) for oscillations in iEEG (resp. MEG). A subset of SOZ regions were detected by one type of discharges but not the other (25 % for spikes and 8 % for oscillations). Our study suggests that spike and oscillatory activities involve overlapping but distinct networks, and are complementary for presurgical mapping.

Interictal networks in magnetoencephalography.

Epileptic networks involve complex relationships across several brain areas. Such networks have been shown on intracerebral EEG (stereotaxic EEG, SEEG), an invasive technique. Magnetoencephalography (MEG) is a noninvasive tool, which was recently proven to be efficient for localizing the generators of epileptiform discharges. However, despite the importance of characterizing non-invasively network aspects in partial epilepsies, only few studies have attempted to retrieve fine spatiotemporal dynamics of interictal discharges with MEG. Our goal was to assess the relevance of magnetoencephalography for detecting and characterizing the brain networks involved in interictal epileptic discharges. We propose here a semi-automatic method based on independent component analysis (ICA) and on co-occurrence of events across components. The method was evaluated in a series of seven patients by comparing its results with networks identified in SEEG. On both MEG and SEEG, we found that interictal discharges can involve remote regions which are acting in synchrony. More regions were identified in SEEG (38 in total) than in MEG (20). All MEG regions were confirmed by SEEG when an electrode was present in the vicinity. In all patients, at least one region could be identified as leading according to our criteria. A majority (71%) of MEG leaders were confirmed by SEEG. We have therefore shown that MEG measurements can extract a significant proportion of the networks visible in SEEG. This suggests that MEG can be a useful tool for defining noninvasively interictal epileptic networks, in terms of regions and patterns of connectivity, in search for a "primary irritative zone".

Asleep but aware?

Despite sleep-induced drastic decrease of self-awareness, human sleep allows some cognitive processing of external stimuli. Here we report the fortuitous observation in a patient who, while being recorded with intra-cerebral electrodes, was able, during paradoxical sleep, to reproduce a motor behaviour previously performed at wake to consciously indicate her perception of nociceptive stimulation. Noxious stimuli induced behavioural responses only if they reached the cortex during periods when mid-frontal networks (pre-SMA, pre-motor cortex) were pre-activated. Sensory responses in the opercular cortex and insula were identical whether the noxious stimulus was to evoke or not a motor behaviour; conversely, the responses in mid-anterior cingulate were specifically enhanced for stimuli yielding motor responses. Neuronal networks implicated in the voluntary preparation of movements may be reactivated during paradoxical sleep, but only if behavioural-relevant stimuli reach the cortex during specific periods of "motor awareness". These local activation appeared without any global sleep stage change. This observation opens the way to further studies on the currently unknown capacity of the sleeping brain to interact meaningfully with its environment.

What do intracerebral electrodes measure?

OBJECTIVE: Gain insight and improve our interpretation of measurements from intracerebral electrodes. Determine if interpretation of intracerebral EEG is dependent on electrode characteristics. METHODS: We use intracerebral EEG measurements differing only in the recording electrodes (Dixi or homemade electrodes), and numerical simulations to determine the spatial sensitivity of intracerebral electrodes and its dependence on several parameters. RESULTS: There is a difference in the high frequency (>20 Hz) power depending on the electrode type, which cannot be explained by the different contact sizes or distance between contacts. Simulations show that the width of the gap between electrode and brain and the extent of the generators have an effect on sensitivity, while other parameters are less important. CONCLUSIONS: The sensitivity of intracerebral electrodes is not affected in an important way by the dimensions of the contacts, but depends on the extent of generators. The unusual insertion technique of homemade electrodes resulting in a large gap between functional brain and electrodes, explains the observed signal difference. SIGNIFICANCE: Numerical simulation is a useful tool in the choice or design of intracerebral electrodes, and increases our understanding of their measurements. The interpretation of intracerebral EEG is not affected by differences between typical commercially available electrodes.

A Platform for Cognitive Monitoring of Neurosurgical Patients During Hospitalization.

Intracranial recordings in epilepsy patients are increasingly utilized to gain insight into the electrophysiological mechanisms of human cognition. There are currently several practical limitations to conducting research with these patients, including patient and researcher availability and the cognitive abilities of patients, which limit the amount of task-related data that can be collected. Prior studies have synchronized clinical audio, video, and neural recordings to understand naturalistic behaviors, but these recordings are centered on the patient to understand their seizure semiology and thus do not capture and synchronize audiovisual stimuli experienced by patients. Here, we describe a platform for cognitive monitoring of neurosurgical patients during their hospitalization that benefits both patients and researchers. We provide the full specifications for this system and describe some example use cases in perception, memory, and sleep research. We provide results obtained from a patient passively watching TV as proof-of-principle for the naturalistic study of cognition. Our system opens up new avenues to collect more data per patient using real-world behaviors, affording new possibilities to conduct longitudinal studies of the electrophysiological basis of human cognition under naturalistic conditions.

Could we have missed out the seizure onset: A study based on intracranial EEG.

OBJECTIVE: Intracranial EEG covers only a small fraction of brain volume and it is uncertain if a discharge represents a true seizure onset or results from spread. We therefore assessed if there are differences between characteristics of the ictal onset when we are likely to have a true onset, and characteristics of the discharge in regions of spread. METHODS: Wavelet based statistical features were extracted in 503 onset and 390 spread channels of 58 seizures from 20 patients. These features were used as predictors in models based on machine learning algorithms such as k-nearest neighbour, logistic regression, multilayer perceptron, support vector machine, random and rotation forest. RESULTS: Statistical features (mean, variance, skewness and kurtosis) associated with all wavelet scales were significantly higher in onset than in spread channels. The best classifier, random forest, achieved accuracy of 79.6% and precision of 82%. CONCLUSIONS: The signals associated with onset and spread regions exhibit different characteristics. The proposed features are able to classify the signals with good accuracy. SIGNIFICANCE: Using our classifier on new seizures could help clinicians gain confidence in having recorded the real seizure onset or on the contrary be concerned that the true onset may have been missed.

Prediction of secondary generalization from a focal onset seizure in intracerebral EEG.

OBJECTIVE: We propose a system based on the first five seconds of intracerebrally recorded focal seizures to predict their evolution from focal to bilateral tonic-clonic seizure (FTC), to spread outside the onset zone but without tonic-clonic component (FS), or to a seizure remaining focal (F). METHODS: Nineteen time and frequency domain features were extracted from 39 seizures of 32 patients and were subjected to support vector machine based classification. Three prediction approaches regarding seizure evolution were (1) FTC vs FS vs F, (2) FTC vs FS or F and (3) FTC or FS vs F. RESULTS: We used 21 seizures for training. Most features had significantly different distributions in the three seizure types (p < 0.05). Eighteen seizures were used for testing. We predicted the evolution of 12 seizures in FTC vs FS vs F, 13 seizures in FTC vs FS or F and 14 seizures in FTC or FS vs F. CONCLUSION: The first five seconds of a focal seizure contains information regarding the eventual evolution of the seizure, which could be predicted in most seizures. SIGNIFICANCE: The proposed system could alert the health care team when a patient is hospitalized for intracerebral EEG and improve safety and eventually result in an implantable device.

Sharply contoured theta waves are the human correlate of ponto-geniculo-occipital waves in the primary visual cortex.

OBJECTIVE: Ponto-geniculo-occipital (PGO) waves occurring along the visual axis are one of the hallmarks of REM sleep in experimental animals. In humans, direct evidence is scarce. There is no systematic study of PGO waves in the primary visual cortex. METHODS: Eleven epilepsy patients undergoing combined intracranial EEG/polysomnography had 71 channels recording physiological EEG activity from various cortical areas; seven channels recorded from the primary visual cortex. An equal number of 4-s phasic and tonic REM segments were selected. Patterns consistent with PGO waves were visually analyzed in both states in the primary visual cortex. Spectral analysis compared activity in the primary visual cortex with the remaining cortical areas. RESULTS: Visual inspection revealed an increase in sharply contoured theta waves (duration: 150-250 ms) in the primary visual cortex during phasic as compared to tonic REM sleep. Spectral analysis confirmed a 32% increase in mean absolute theta power during phasic versus tonic REM sleep (p corrected = 0.014). CONCLUSION: No classical PGO waves, but sharply contoured theta waves were found in the human primary visual cortex during phasic as opposed to tonic REM sleep. SIGNIFICANCE: This research suggests that sharply contoured theta waves are the human correlate of PGO waves described in experimental animal models.

Physiological and pathological high-frequency oscillations have distinct sleep-homeostatic properties.

OBJECTIVE: The stage of sleep is a known modulator of high-frequency oscillations (HFOs). For instance, high amplitude slow waves during NREM sleep and the subtypes of REM sleep were shown to contribute to a better separation between physiological and pathological HFOs. This study investigated rates and spatial spread of the different HFO types (physiological and pathological ripples in the 80-250 Hz frequency band, and fast ripples above 250 Hz) depending on time spent in sleep across the different sleep cycles. METHODS: Fifteen patients with focal pharmaco-resistant epilepsy underwent one night of video-polysomnography during chronic intracranial EEG recording for presurgical epilepsy evaluation. The HFO rate and spread across the different sleep cycles were determined with an automatic HFO detector. We built models to explain the observed rate and spread based on time in sleep and other variables i.e. sleep stage, delta band and sigma band activity, and slow wave amplitude. Statistical significance of the different variables was determined by a model comparison using the Akaike information criterion. RESULTS: The rate of HFOs depends significantly on the accumulated time of sleep. As the night advanced, the rate of pathological ripples and fast ripples decreased during NREM sleep (up to 15% per hour spent in the respective sleep stages), while the rate of physiological ripples increased during REM sleep (8% per hour spent in REM sleep). Interestingly, the stage of sleep but not the sleep cycle determined the extent of spread of HFOs, showing a larger field during NREM sleep and a more restricted field during REM sleep. CONCLUSION: The different dependence with sleep time for physiological and pathological ripples is in keeping with their distinct underlying generating mechanisms. From a practical point of view, the first sleep cycle seems to be best suitable for studying HFOs in epilepsy, given that the contrast between physiological and pathological ripple rates is largest during this time.