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1.
Epilepsia ; 65(4): 961-973, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38306118

ABSTRACT

OBJECTIVE: Genetic generalized epilepsy (GGE) accounts for approximately 20% of adult epilepsy cases and is considered a disorder of large brain networks, involving both hemispheres. Most studies have not shown any difference in functional whole-brain network topology when compared to healthy controls. Our objective was to examine whether this preserved global network topology could hide local reorganizations that balance out at the global network level. METHODS: We recorded high-density electroencephalograms from 20 patients and 20 controls, and reconstructed the activity of 118 regions. We computed functional connectivity in windows free of interictal epileptiform discharges in broad, delta, theta, alpha, and beta frequency bands, characterized the network topology, and used the Hub Disruption Index (HDI) to quantify the topological reorganization. We examined the generalizability of our results by reproducing a 25-electrode clinical system. RESULTS: Our study did not reveal any significant change in whole-brain network topology among GGE patients. However, the HDI was significantly different between patients and controls in all frequency bands except alpha (p < .01, false discovery rate [FDR] corrected, d < -1), and accompanied by an increase in connectivity in the prefrontal regions and default mode network. This reorganization suggests that regions that are important in transferring the information in controls were less so in patients. Inversely, the crucial regions in patients are less so in controls. These findings were also found in delta and theta frequency bands when using 25 electrodes (p < .001, FDR corrected, d < -1). SIGNIFICANCE: In GGE patients, the overall network topology is similar to that of healthy controls but presents a balanced local topological reorganization. This reorganization causes the prefrontal areas and default mode network to be more integrated and segregated, which may explain executive impairment associated with GGE. Additionally, the reorganization distinguishes patients from controls even when using 25 electrodes, suggesting its potential use as a diagnostic tool.


Subject(s)
Epilepsy, Generalized , Epilepsy , Adult , Humans , Nerve Net/diagnostic imaging , Brain/diagnostic imaging , Electroencephalography/methods , Brain Mapping , Epilepsy, Generalized/genetics , Magnetic Resonance Imaging/methods
2.
Epilepsia ; 63(4): 961-973, 2022 04.
Article in English | MEDLINE | ID: mdl-35048363

ABSTRACT

OBJECTIVE: Nodular heterotopias (NHs) are malformations of cortical development associated with drug-resistant focal epilepsy with frequent poor surgical outcome. The epileptogenic network is complex and can involve the nodule, the overlying cortex, or both. Single-pulse electrical stimulation (SPES) during stereo-electroencephalography (SEEG) allows the investigation of functional connectivity between the stimulated and responsive cortices by eliciting cortico-cortical evoked potentials (CCEPs). We used SPES to analyze the NH connectome and its relation to the epileptogenic network organization. METHODS: We retrospectively studied 12 patients with NH who underwent 1 Hz or 0.2 Hz SPES of NH during SEEG. Outbound connectivity (regions where CCEPs were elicited by NH stimulation) and inbound connectivity (regions where stimulation elicited CCEPs in the NH) were searched. SEEG channels were then classified as "heterotopic" (located within the NH), "connected" (located in normotopic cortex and showing connectivity with the NH), and "unconnected." We used the epileptogenicity index (EI) to quantify implication of channels in the seizure-onset zone and to classify seizures as heterotopic, normotopic, and normo-heterotopic. RESULTS: One hundred thirty-five outbound and 72 inbound connections were found. Three patients showed connectivity between hippocampus and NH, and seven patients showed strong internodular connectivity. A total of 39 seizures were analyzed: 23 normo-heterotopic, 12 normotopic, and 4 heterotopic. Logistic regression found that "connected" channels were significantly (p = 8.4e-05) more likely to be epileptogenic than "unconnected" channels (odds ratio 4.71, 95% confidence interval (CI) [2.17, 10.21]) and heterotopic channels were also significantly (p = .024) more epileptogenic than "unconnected" channels (odds ratio 3.29, 95% CI [1.17, 9.23]). SIGNIFICANCE: SPES reveals widespread connectivity between NH and normotopic regions. Those connected regions show higher epileptogenicity. SPES might be useful to assess NH epileptogenic network.


Subject(s)
Choristoma , Drug Resistant Epilepsy , Epilepsy , Choristoma/complications , Drug Resistant Epilepsy/complications , Drug Resistant Epilepsy/diagnostic imaging , Drug Resistant Epilepsy/surgery , Electric Stimulation , Electroencephalography , Evoked Potentials/physiology , Humans , Retrospective Studies , Seizures/complications
3.
Brain Topogr ; 35(2): 191-206, 2022 03.
Article in English | MEDLINE | ID: mdl-35080692

ABSTRACT

Episodic autobiographical memory (EAM) is a complex cognitive function that emerges from the coordination of specific and distant brain regions. Specific brain rhythms, namely theta and gamma oscillations and their synchronization, are thought of as putative mechanisms enabling EAM. Yet, the mechanisms of inter-regional interaction in the EAM network remain unclear in humans at the whole brain level. To investigate this, we analyzed EEG recordings of participants instructed to retrieve autobiographical episodes. EEG recordings were projected in the source space, and time-courses of atlas-based brain regions-of-interest (ROIs) were derived. Directed phase synchrony in high theta (7-10 Hz) and gamma (30-80 Hz) bands and high theta-gamma phase-amplitude coupling were computed between each pair of ROIs. Using network-based statistics, a graph-theory method, we found statistically significant networks for each investigated mechanism. In the gamma band, two sub-networks were found, one between the posterior cingulate cortex (PCC) and the medial temporal lobe (MTL) and another within the medial frontal areas. In the high theta band, we found a PCC to ventromedial prefrontal cortex (vmPFC) network. In phase-amplitude coupling, we found the high theta phase of the left MTL biasing the gamma amplitude of posterior regions and the vmPFC. Other regions of the temporal lobe and the insula were also phase biasing the vmPFC. These findings suggest that EAM, rather than emerging from a single mechanism at a single frequency, involves precise spatio-temporal signatures mapping on distinct memory processes. We propose that the MTL orchestrates activity in vmPFC and PCC via precise phase-amplitude coupling, with vmPFC and PCC interaction via high theta phase synchrony and gamma synchronization contributing to bind information within the PCC-MTL sub-network or valuate the candidate memory within the medial frontal sub-network.


Subject(s)
Memory, Episodic , Brain , Brain Mapping , Humans , Mental Recall , Prefrontal Cortex , Temporal Lobe , Theta Rhythm
4.
Ann Neurol ; 87(6): 976-987, 2020 06.
Article in English | MEDLINE | ID: mdl-32279329

ABSTRACT

OBJECTIVE: Non-rapid eye movement (NREM) sleep is supposed to play a key role in long-term memory consolidation transferring information from hippocampus to neocortex. However, sleep also activates epileptic activities in medial temporal regions. This study investigated whether interictal hippocampal spikes during sleep would impair long-term memory consolidation. METHOD: We prospectively measured visual and verbal memory performance in 20 patients with epilepsy investigated with stereoelectroencephalography (SEEG) at immediate, 30-minute, and 1-week delays, and studied the correlations between interictal hippocampal spike frequency during waking and the first cycle of NREM sleep and memory performance, taking into account the number of seizures occurring during the consolidation period and other possible confounding factors, such as age and epilepsy duration. RESULTS: Retention of verbal memory over 1 week was negatively correlated with hippocampal spike frequency during sleep, whereas no significant correlation was found with hippocampal interictal spikes during waking. No significant result was found for visual memory. Regression tree analysis showed that the number of seizures was the first factor that impaired the verbal memory retention between 30 minutes and 1 week. When the number of seizures was below 5, spike frequency during sleep higher than 13 minutes was associated with impaired memory retention over 1 week. INTERPRETATION: Our results show that activation of interictal spikes in the hippocampus during sleep and seizures specifically impair long-term memory consolidation. We hypothesize that hippocampal interictal spikes during sleep interrupt hippocampal-neocortical transfer of information. ANN NEUROL 2020;87:976-987.


Subject(s)
Hippocampus/physiopathology , Memory Consolidation , Memory, Long-Term , Seizures/physiopathology , Seizures/psychology , Sleep , Adolescent , Adult , Electroencephalography , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Prospective Studies , Psychomotor Performance , Sleep, Slow-Wave , Verbal Learning , Young Adult
5.
Epilepsia ; 62(9): 2048-2059, 2021 09.
Article in English | MEDLINE | ID: mdl-34272883

ABSTRACT

OBJECTIVE: Stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) aims at modifying epileptogenic networks to reduce seizure frequency. High-frequency oscillations (HFOs), spikes, and cross-rate are quantifiable epileptogenic biomarkers. In this study, we sought to evaluate, using SEEG signals recorded before and after thermocoagulation, whether a variation in these markers is related to the therapeutic effect of this procedure and to the outcome of surgery. METHODS: Interictal segments of SEEG signals were analyzed in 38 patients during presurgical evaluation. We used an automatized method to quantify the rate of spikes, rate of HFOs, and cross-rate (a measure combining spikes and HFOs) before and after thermocoagulation. We analyzed the differences both at an individual level with a surrogate approach and at a group level with analysis of variance. We then evaluated the correlation between these variations and the clinical response to RF-TC and to subsequent resective surgery. RESULTS: After thermocoagulation, 19 patients showed a clinical improvement. At the individual level, clinically improved patients more frequently had a reduction in spikes and cross-rate in the epileptogenic zone than patients without clinical improvement (p = .002, p = .02). At a group level, there was a greater decrease of HFOs in epileptogenic and thermocoagulated zones in patients with clinical improvement (p < .05) compared to those with no clinical benefit. Eventually, a significant decrease of all the markers after RF-TC was found in patients with a favorable outcome of resective surgery (spikes, p = .026; HFOs, p = .03; cross-rate, p = .03). SIGNIFICANCE: Quantified changes in the rate of spikes, rate of HFOs, and cross-rate can be observed after thermocoagulation, and the reduction of these markers correlates with a favorable clinical outcome after RF-TC and with successful resective surgery. This may suggest that interictal biomarker modifications after RF-TC can be clinically used to predict the effectiveness of the thermocoagulation procedure and the outcome of resective surgery.


Subject(s)
Electrocoagulation , Electroencephalography , Biomarkers , Humans , Imaging, Three-Dimensional , Seizures , Treatment Outcome
7.
Curr Opin Neurol ; 32(2): 213-219, 2019 04.
Article in English | MEDLINE | ID: mdl-30694920

ABSTRACT

PURPOSE OF REVIEW: Precise localization of the epileptogenic zone is imperative for the success of resective surgery of drug-resistant epileptic patients. To decrease the number of surgical failures, clinical research has been focusing on finding new biomarkers. For the past decades, high-frequency oscillations (HFOs, 80-500 Hz) have ousted interictal spikes - the classical interictal marker - from the research spotlight. Many studies have claimed that HFOs were more linked to epileptogenicity than spikes. This present review aims at refining this statement in light of recent studies. RECENT FINDINGS: Analysis based on single-patient characteristics has not been able to determine which of HFOs or spikes were better marker of epileptogenic tissues. Physiological HFOs are one of the main obstacles to translate HFOs to clinical practice as separating them from pathological HFOs remains a challenge. Fast ripples (a subgroup of HFOs, 250-500 Hz) which are mostly pathological are not found in all epileptogenic tissues. SUMMARY: Quantified measures of HFOs and spikes give complementary results, but many barriers still persist in applying them in clinical routine. The current way of testing HFO and spike detectors and their performance in delineating the epileptogenic zone is debatable and still lacks practicality. Solutions to handle physiological HFOs have been proposed but are still at a preliminary stage.


Subject(s)
Biomarkers , Brain/physiopathology , Drug Resistant Epilepsy/diagnosis , Electroencephalography/methods , Brain Mapping , Drug Resistant Epilepsy/classification , Drug Resistant Epilepsy/physiopathology , Electroencephalography/classification , Humans
8.
Ann Neurol ; 83(1): 84-97, 2018 01.
Article in English | MEDLINE | ID: mdl-29244226

ABSTRACT

OBJECTIVE: High-frequency oscillations (HFOs) in intracerebral EEG (stereoelectroencephalography; SEEG) are considered as better biomarkers of epileptogenic tissues than spikes. How this can be applied at the patient level remains poorly understood. We investigated how well HFOs and spikes can predict epileptogenic regions with a large spatial sampling at the patient level. METHODS: We analyzed non-REM sleep SEEG recordings sampled at 2,048Hz of 30 patients. Ripples (Rs; 80-250Hz), fast ripples (FRs; 250-500Hz), and spikes were automatically detected. Rates of these markers and several combinations-spikes co-occurring with HFOs or FRs and cross-rate (Spk⊗HFO)-were compared to a quantified measure of the seizure onset zone (SOZ) by performing a receiver operating characteristic analysis for each patient individually. We used a Wilcoxon signed-rank test corrected for false-discovery rate to assess whether a marker was better than the others for predicting the SOZ. RESULTS: A total of 2,930 channels was analyzed (median of 100 channels per patient). The HFOs or any of its variants were not statistically better than spikes. Only one feature, the cross-rate, was better than all the other markers. Moreover, fast ripples, even though very specific, were not delineating all epileptogenic tissues. INTERPRETATION: At the patient level, the performance of HFOs is weakened by the presence of strong physiological HFO generators. Fast ripples are not sensitive enough to be the unique biomarker of epileptogenicity. Nevertheless, combining HFOs and spikes using our proposed measure-the cross-rate-is a better strategy than using only one marker. Ann Neurol 2018;83:84-97.


Subject(s)
Electroencephalography , Epilepsy/diagnosis , Adult , Automation , Biomarkers , Brain Mapping , Female , Humans , Male , Predictive Value of Tests , Seizures/physiopathology , Sleep, Slow-Wave
9.
Brain ; 141(10): 2966-2980, 2018 10 01.
Article in English | MEDLINE | ID: mdl-30107499

ABSTRACT

Drug-refractory focal epilepsies are network diseases associated with functional connectivity alterations both during ictal and interictal periods. A large majority of studies on the interictal/resting state have focused on functional MRI-based functional connectivity. Few studies have used electrophysiology, despite its high temporal capacities. In particular, stereotactic-EEG is highly suitable to study functional connectivity because it permits direct intracranial electrophysiological recordings with relative large-scale sampling. Most previous studies in stereotactic-EEG have been directed towards temporal lobe epilepsy, which does not represent the whole spectrum of drug-refractory epilepsies. The present study aims at filling this gap, investigating interictal functional connectivity alterations behind cortical epileptic organization and its association with post-surgical prognosis. To this purpose, we studied a large cohort of 59 patients with malformation of cortical development explored by stereotactic-EEG with a wide spatial sampling (76 distinct brain areas were recorded, median of 13.2 per patient). We computed functional connectivity using non-linear correlation. We focused on three zones defined by stereotactic-EEG ictal activity: the epileptogenic zone, the propagation zone and the non-involved zone. First, we compared within-zone and between-zones functional connectivity. Second, we analysed the directionality of functional connectivity between these zones. Third, we measured the associations between functional connectivity measures and clinical variables, especially post-surgical prognosis. Our study confirms that functional connectivity differs according to the zone under investigation. We found: (i) a gradual decrease of the within-zone functional connectivity with higher values for epileptogenic zone and propagation zone, and lower for non-involved zones; (ii) preferential coupling between structures of the epileptogenic zone; (iii) preferential coupling between epileptogenic zone and propagation zone; and (iv) poorer post-surgical outcome in patients with higher functional connectivity of non-involved zone (within- non-involved zone, between non-involved zone and propagation zone functional connectivity). Our work suggests that, even during the interictal state, functional connectivity is reinforced within epileptic cortices (epileptogenic zone and propagation zone) with a gradual organization. Moreover, larger functional connectivity alterations, suggesting more diffuse disease, are associated with poorer post-surgical prognosis. This is consistent with computational studies suggesting that connectivity is crucial in order to model the spatiotemporal dynamics of seizures.10.1093/brain/awy214_video1awy214media15833456182001.


Subject(s)
Brain/physiopathology , Drug Resistant Epilepsy/physiopathology , Epilepsies, Partial/physiopathology , Neural Pathways/physiopathology , Adolescent , Adult , Child , Child, Preschool , Drug Resistant Epilepsy/etiology , Electroencephalography , Epilepsies, Partial/etiology , Female , Humans , Infant , Infant, Newborn , Male , Malformations of Cortical Development/complications , Malformations of Cortical Development/physiopathology , Nerve Net/physiopathology , Stereotaxic Techniques , Young Adult
10.
Epilepsia ; 59(1): 235-243, 2018 01.
Article in English | MEDLINE | ID: mdl-29205292

ABSTRACT

OBJECTIVE: Non-rapid eye movement (NREM) sleep is known to be a brain state associated with an activation of interictal epileptic activity. The goal of this work was to quantify topographic changes occurring during NREM sleep in comparison with wakefulness. METHOD: We studied intracerebral recordings of 20 patients who underwent stereo-electroencephalography (SEEG) during presurgical evaluation for pharmacoresistant focal epilepsy. We measured the number of interictal spikes (IS) and quantified the co-occurrence of IS between brain regions during 1 hour of NREM sleep and 1 hour of wakefulness. Co-occurrence is a method to estimate IS networks based on a temporal concordance between IS of different brain regions. Each studied region was labeled as "seizure-onset zone" (SOZ), "propagation zone" (PZ), or "not involved region" (NIR). RESULTS: During NREM sleep, the number of interictal spikes significantly increased in all regions (mean of 68%). This increase was higher in medial temporal regions than in other regions, whether involved in the SOZ. Spike co-occurrence increased significantly in all regions during NREM sleep in comparison with wakefulness but was greater in neocortical regions. Spike co-occurrence in medial temporal regions was not higher than in other regions, suggesting that the increase of the number of spikes in this region was in great part a local effect. SIGNIFICANCE: This study demonstrated that medial temporal regions show a greater propensity to spike production or propagation during NREM sleep compared to other brain regions, even when the medial temporal lobe is not involved in the SOZ.


Subject(s)
Brain Waves/physiology , Drug Resistant Epilepsy/physiopathology , Sleep Stages/physiology , Wakefulness/physiology , Adolescent , Adult , Analysis of Variance , Brain/physiopathology , Drug Resistant Epilepsy/pathology , Electroencephalography , Female , Functional Laterality , Humans , Male , Middle Aged , Young Adult
11.
Epilepsy Behav ; 88: 262-267, 2018 11.
Article in English | MEDLINE | ID: mdl-30317060

ABSTRACT

OBJECTIVES: The objective of the study was to describe electroclinical patterns in habitual seizures with motor semiology at onset, triggered by diagnostic stimulation, in patients undergoing presurgical evaluation using stereoelectroencephalography (SEEG). METHODS: Seizure semiology, stimulation parameters, electroclinical data, and anatomical localization were evaluated in stimulated and spontaneous seizures. RESULTS: From 120 habitual seizures triggered by 50-Hz train bipolar stimulation during SEEG, 20 presented initial motor semiology (elementary motor signs, complex motor behavior, or both). Two patterns occurred: long latency onset (7/20), where semiology occurred after the stimulation train, following visible cortical epileptic discharge similarly to spontaneous seizures; and short latency onset (13/20), in which typical semiological expression occurred during the stimulation train, preceding typical cortical discharge. CONCLUSIONS: This novel observation shows that in some conditions, seizures with habitual motor semiology could be triggered early during stimulation, before typical cortical epileptic discharge became visible. The earliness of clinical onset with regard to visible cortical discharge, notably in comparison with clinically similar spontaneous seizures, suggests differences in electrophysiological mechanisms that require further investigation. These may involve preferential involvement of descending corticosubcortical connections within the same epileptogenic network for a given patient.


Subject(s)
Cerebral Cortex/physiopathology , Electroencephalography/methods , Seizures/diagnosis , Seizures/physiopathology , Stereotaxic Techniques , Adolescent , Adult , Child , Early Diagnosis , Electrophysiological Phenomena/physiology , Female , Humans , Male , Middle Aged , Young Adult
12.
Epilepsia ; 58(12): 2112-2123, 2017 12.
Article in English | MEDLINE | ID: mdl-28983921

ABSTRACT

OBJECTIVE: Defining the roles of heterotopic and normotopic cortex in the epileptogenic networks in patients with nodular heterotopia is challenging. To elucidate this issue, we compared heterotopic and normotopic cortex using quantitative signal analysis on stereoelectroencephalography (SEEG) recordings. METHODS: Clinically relevant biomarkers of epileptogenicity during ictal (epileptogenicity index; EI) and interictal recordings (high-frequency oscillation and spike) were evaluated in 19 patients undergoing SEEG. These biomarkers were then compared between heterotopic cortex and neocortical regions. Seizures were classified as normotopic, heterotopic, or normoheterotopic according to respective values of quantitative analysis (EI ≥0.3). RESULTS: A total of 1,246 contacts were analyzed: 259 in heterotopic tissue (heterotopic cortex), 873 in neocortex in the same lobe of the lesion (local neocortex), and 114 in neocortex distant from the lesion (distant neocortex). No significant difference in EI values, high-frequency oscillations, and spike rate was found comparing local neocortex and heterotopic cortex at a patient level, but local neocortex appears more epileptogenic (p < 0.001) than heterotopic cortex analyzing EI values at a seizure level. According to EI values, seizures were mostly normotopic (48.5%) or normoheterotopic (45.5%); only 6% were purely heterotopic. A good long-term treatment response was obtained in only two patients after thermocoagulation and surgical disconnection. SIGNIFICANCE: This is the first quantitative SEEG study providing insight into the mechanisms generating seizures in nodular heterotopia. We demonstrate that both the heterotopic lesion and particularly the normotopic cortex are involved in the epileptogenic network. This could open new perspectives on multitarget treatments, other than resective surgery, aimed at modifying the epileptic network.


Subject(s)
Cerebral Cortex , Choristoma/physiopathology , Electroencephalography/methods , Epilepsy/physiopathology , Adolescent , Adult , Age of Onset , Biomarkers , Child , Choristoma/complications , Choristoma/surgery , Cohort Studies , Electrocoagulation , Epilepsy/etiology , Epilepsy/surgery , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nerve Net/physiopathology , Nerve Net/surgery , Neurosurgical Procedures , Seizures/physiopathology , Young Adult
14.
J Neurosci Methods ; 408: 110160, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38734149

ABSTRACT

Simultaneous noninvasive and invasive electrophysiological recordings provide a unique opportunity to achieve a comprehensive understanding of human brain activity, much like a Rosetta stone for human neuroscience. In this review we focus on the increasingly-used powerful combination of intracranial electroencephalography (iEEG) with scalp electroencephalography (EEG) or magnetoencephalography (MEG). We first provide practical insight on how to achieve these technically challenging recordings. We then provide examples from clinical research on how simultaneous recordings are advancing our understanding of epilepsy. This is followed by the illustration of how human neuroscience and methodological advances could benefit from these simultaneous recordings. We conclude with a call for open data sharing and collaboration, while ensuring neuroethical approaches and argue that only with a true collaborative approach the promises of simultaneous recordings will be fulfilled.


Subject(s)
Brain , Magnetoencephalography , Humans , Magnetoencephalography/methods , Brain/physiology , Electroencephalography/methods , Epilepsy/physiopathology , Electrocorticography/methods
15.
Brain Commun ; 5(3): fcad161, 2023.
Article in English | MEDLINE | ID: mdl-37292455

ABSTRACT

Sleep can modulate epileptic activities, but our knowledge of sleep perturbation by epilepsy remains sparse. Interestingly, epilepsy and sleep both present with defining electrophysiological features in the form of specific graphoelements on EEG. This raises the possibility to identify, within ongoing EEG activity, how epilepsy impacts and disrupts sleep. Here, we asked whether the presence of a lateralized epileptic focus interferes with the expression of the dominant electrophysiological hallmarks of sleep: slow oscillations, slow waves and spindles. To this aim, we conducted a cross-sectional study and analysed sleep recordings with surface EEG from 69 patients with focal epilepsy (age range at EEG: 17-61 years, 29 females, 34 left focal epilepsy). Comparing patients with left and right focal epilepsy, we assessed inter-hemispheric asymmetry of sleep slow oscillations power (delta range, 0.5-4 Hz); sleep slow wave density; amplitude, duration and slope; and spindle density, amplitude, duration as well as locking to slow oscillations. We found significantly different asymmetries in slow oscillation power (P < 0.01); slow wave amplitude (P < 0.05) and slope (P < 0.01); and spindle density (P < 0.0001) and amplitude (P < 0.05). To confirm that these population-based differences reflect actual patient-by-patient differences, we then tested whether asymmetry of sleep features can classify laterality of the epileptic focus using a decision tree and a 5-fold cross-validation. We show that classification accuracy is above chance level (accuracy of 65%, standard deviation: 5%) and significantly outperforms a classification based on a randomization of epileptic lateralization (randomization data accuracy: 50%, standard deviation 7%, unpaired t-test, P < 0.0001). Importantly, we show that classification of epileptic lateralization by the canonical epileptic biomarker, i.e. interictal epileptiform discharges, improves slightly but significantly when combined with electrophysiological hallmarks of physiological sleep (from 75% to 77%, P < 0.0001, one-way ANOVA + Sidak's multiple comparisons test). Together, we establish that epilepsy is associated with inter-hemispheric perturbation of sleep-related activities and provide an in-depth multi-dimensional profile of the main sleep electrophysiological signatures in a large cohort of patients with focal epilepsy. We provide converging evidence that the underlying epileptic process interacts with the expression of sleep markers, in addition to triggering well-known pathological activities, such as interictal epileptiform discharges.

16.
Clin Neurophysiol ; 143: 84-94, 2022 11.
Article in English | MEDLINE | ID: mdl-36166901

ABSTRACT

OBJECTIVE: To study changes of thalamo-cortical and cortico-cortical connectivity during wakefulness, non-Rapid Eye Movement (non-REM) sleep, including N2 and N3 stages, and REM sleep, using stereoelectroencephalography (SEEG) recording in humans. METHODS: We studied SEEG recordings of ten patients during wakefulness, non-REM sleep and REM sleep, in seven brain regions of interest including the thalamus. We calculated directed and undirected functional connectivity using a measure of non-linear correlation coefficient h2. RESULTS: The thalamus was more connected to other brain regions during N2 stage and REM sleep than during N3 stage during which cortex was more connected than the thalamus. We found two significant directed links: the first from the prefrontal region to the lateral parietal region in the delta band during N3 sleep and the second from the thalamus to the insula during REM sleep. CONCLUSIONS: These results showed that cortico-cortical connectivity is more prominent in N3 stage than in N2 and REM sleep. During REM sleep we found significant thalamo-insular connectivity, with a driving role of the thalamus. SIGNIFICANCE: We found a pattern of cortical connectivity during N3 sleep concordant with antero-posterior traveling slow waves. The thalamus seemed particularly involved as a hub of connectivity during REM sleep.


Subject(s)
Electroencephalography , Sleep, REM , Electroencephalography/methods , Humans , Sleep/physiology , Sleep, REM/physiology , Thalamus/physiology , Wakefulness/physiology
17.
Am J Psychiatry ; 179(3): 204-215, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35236117

ABSTRACT

OBJECTIVE: Brain oscillations play a pivotal role in synchronizing responses of local and global ensembles of neurons. Patients with schizophrenia exhibit impairments in oscillatory response, which are thought to stem from abnormal maturation during critical developmental stages. Studying individuals at genetic risk for psychosis, such as 22q11.2 deletion carriers, from childhood to adulthood may provide insights into developmental abnormalities. METHODS: The authors acquired 106 consecutive T1-weighted MR images and 40-Hz auditory steady-state responses (ASSRs) with high-density (256 channel) EEG in a group of 58 22q11.2 deletion carriers and 48 healthy control subjects. ASSRs were analyzed with 1) time-frequency analysis using Morlet wavelet decomposition, 2) intertrial phase coherence (ITPC), and 3) theta-gamma phase-amplitude coupling estimated in the source space between brain regions activated by the ASSRs. Additionally, volumetric analyses were performed with FreeSurfer. Subanalyses were conducted in deletion carriers who endorsed psychotic symptoms and in subgroups with different age bins. RESULTS: Deletion carriers had decreased theta and late-latency 40-Hz ASSRs and phase synchronization compared with control subjects. Deletion carriers with psychotic symptoms displayed a further reduction of gamma-band response, decreased ITPC, and decreased top-down modulation of gamma-band response in the auditory cortex. Reduced gamma-band response was correlated with the atrophy of auditory cortex in individuals with psychotic symptoms. In addition, a linear increase of theta and gamma power from childhood to adulthood was found in control subjects but not in deletion carriers. CONCLUSIONS: The results suggest that while all deletion carriers exhibit decreased gamma-band response, more severe local and long-range communication abnormalities are associated with the emergence of psychotic symptoms and gray matter loss. Additionally, the lack of age-related changes in deletion carriers indexes a potential developmental impairment in circuits underlying the maturation of neural oscillations during adolescence. The progressive disruption of gamma-band response in 22q11.2 deletion syndrome supports a developmental perspective toward understanding and treating psychotic disorders.


Subject(s)
Auditory Cortex , DiGeorge Syndrome , Psychotic Disorders , Schizophrenia , Adolescent , Child , Electroencephalography , Humans , Psychotic Disorders/genetics , Schizophrenia/diagnosis , Young Adult
18.
Epilepsy Res ; 169: 106528, 2021 01.
Article in English | MEDLINE | ID: mdl-33360538

ABSTRACT

Skin Conductance Biofeedback (SCB) is a non-invasive behavioral treatment for epilepsy based on modulation of Galvanic Skin Response (GSR). We evaluated changes in functional connectivity occurring after SCB. Six patients with drug-resistant temporal lobe epilepsy underwent monthly SCB sessions. For each patient, 10 min of resting-state magnetoencephalographic (MEG) recording were acquired before and after the first and the last SCB session. For each recording we computed the mean weighted phase lag index (WPLI) across all pair of MEG sensors. After SCB, two patients had consistent reduction of seizure frequency (>50 %). Connectivity analysis revealed a decrease of WPLI-beta band in the two responders and an increase of WPLI-alpha connectivity in all patients regardless of the clinical effect. Results suggest that reduction of WPLI-beta-low connectivity is related to the clinical response after SCB.


Subject(s)
Drug Resistant Epilepsy , Epilepsies, Partial , Biofeedback, Psychology , Drug Resistant Epilepsy/therapy , Humans , Magnetoencephalography , Pharmaceutical Preparations
19.
Neuroinformatics ; 19(4): 639-647, 2021 10.
Article in English | MEDLINE | ID: mdl-33569755

ABSTRACT

Multicentre studies are of utmost importance to confirm hypotheses. The lack of established standards and the ensuing complexity of their data management often hamper their implementation. The Brain Imaging Data Structure (BIDS) is an initiative for organizing and describing neuroimaging and electrophysiological data. Building on BIDS, we have developed two software programs: BIDS Manager and BIDS Uploader. The former has been designed to collect, organise and manage the data and the latter has been conceived to handle their transfer and anonymisation from the partner centres. These two programs aim at facilitating the implementation of multicentre study by providing a standardised framework.


Subject(s)
Brain , Neuroimaging , Brain/diagnostic imaging , Software
20.
Neurology ; 96(2): e280-e293, 2021 01 12.
Article in English | MEDLINE | ID: mdl-33024023

ABSTRACT

OBJECTIVE: To determine the involvement of subcortical regions in human epilepsy by analyzing direct recordings from these regions during epileptic seizures using stereo-EEG (SEEG). METHODS: We studied the SEEG recordings of a large series of patients (74 patients, 157 seizures) with an electrode sampling the thalamus and in some cases also the basal ganglia (caudate nucleus, 22 patients; and putamen, 4 patients). We applied visual analysis and signal quantification methods (Epileptogenicity Index [EI]) to their ictal recordings and compared electrophysiologic with clinical data. RESULTS: We found that in 86% of patients, thalamus was involved during seizures (visual analysis) and 20% showed high values of epileptogenicity (EI >0.3). Basal ganglia may also disclose high values of epileptogenicity (9% in caudate nucleus) but to a lesser degree than thalamus (p < 0.01). We observed different seizure onset patterns including low voltage high frequency activities. We found high values of thalamic epileptogenicity in different epilepsy localizations, including opercular and motor epilepsies. We found no difference between epilepsy etiologies (cryptogenic vs malformation of cortical development, p = 0.77). Thalamic epileptogenicity was correlated with the extension of epileptogenic networks (p = 0.02, ρ 0.32). We found a significant effect (p < 0.05) of thalamic epileptogenicity regarding the postsurgical outcome (higher thalamic EI corresponding to higher probability of surgical failure). CONCLUSIONS: Thalamic involvement during seizures is common in different seizure types. The degree of thalamic epileptogenicity is a possible marker of the epileptogenic network extension and of postsurgical prognosis.


Subject(s)
Basal Ganglia/physiopathology , Electroencephalography/methods , Epilepsies, Partial/physiopathology , Stereotaxic Techniques , Thalamus/physiopathology , Video Recording/methods , Adolescent , Adult , Basal Ganglia/diagnostic imaging , Child , Child, Preschool , Epilepsies, Partial/diagnostic imaging , Female , Humans , Male , Thalamus/diagnostic imaging , Young Adult
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