Publications by authors named "Romain Bouet"

24 Publications

  • Page 1 of 1

Why Are Children So Distractible? Development of Attention and Motor Control From Childhood to Adulthood.

Child Dev 2021 Apr 7. Epub 2021 Apr 7.

INSERM, CNRS, Université Claude Bernard Lyon 1 and Université de Lyon.

Distractibility is the propensity to behaviorally react to irrelevant information. Although children are more distractible the younger they are, the precise contribution of attentional and motor components to distractibility and their developmental trajectories have not been characterized yet. We used a new behavioral paradigm to identify the developmental dynamics of components contributing to distractibility in a large cohort of French participants balanced, between age groups, in gender and socioeconomic status (N = 352; age: 6-25). Results reveal that each measure of these components, namely voluntary attention, distraction, impulsivity, and motor control, present a distinct maturational timeline. In young children, increased distractibility is mostly the result of reduced sustained attention capacities and enhanced distraction, whereas in teenagers, it is the result of decreased motor control and increased impulsivity.
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http://dx.doi.org/10.1111/cdev.13561DOI Listing
April 2021

Relation between coffee consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy.

Epilepsia 2021 Mar 14;62(3):765-777. Epub 2021 Feb 14.

Department of Functional Neurology and Epileptology, Hospices Civils de Lyon and University of Lyon, Lyon, France.

Objective: Caffeine is an antagonist of the adenosine pathway, which is involved in regulation of breathing. Extracellular concentrations of adenosine are increased in the immediate aftermath of a seizure. Seizure-related overstimulation of adenosine receptors might promote peri-ictal apnea. However, the relation between caffeine consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy remains unknown.

Methods: We performed a cross-sectional analysis of data collected in patients included in the SAVE study in Lyon's epilepsy monitoring unit at the Adult Epilepsy Department of the Lyon University Hospital between February 2016 and October 2018. The video-electroencephalographic recordings of 156 patients with drug-resistant focal epilepsy included in the study were reviewed to identify those with ≥1 focal seizure (FS), valid pulse oximetry (SpO ) measurement, and information about usual coffee consumption. This latter was collected at inclusion using a standardized self-questionnaire and further classified into four groups: none, rare (≤3 cups/week), moderate (4 cups/week to 3 cups/day), and high (≥4 cups/day). Peri-ictal hypoxemia (PIH) was defined as SpO < 90% for at least 5 s occurring during the ictal period, the post-ictal period, or both.

Results: Ninety patients fulfilled inclusion criteria, and 323 seizures were analyzed. Both the level of usual coffee consumption (p = .033) and the level of antiepileptic drug withdrawal (p = .004) were independent risk factors for occurrence of PIH. In comparison with FS in patients with no coffee consumption, risk of PIH was four times lower in FS in patients with moderate consumption (odds ratio [OR] = .25, 95% confidence interval [CI] = .07-.91, p = .036) and six times lower in FS in patients with high coffee consumption (OR = .16, 95% CI = .04-.66, p = .011). However, when PIH occurred, its duration was longer in patients with moderate or high consumption than in those with no coffee consumption (p = .042).

Significance: Coffee consumption may be a protective factor for seizure-related respiratory dysfunction, with a dose-dependent effect.
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http://dx.doi.org/10.1111/epi.16837DOI Listing
March 2021

Automatic analysis of single-channel sleep EEG in a large spectrum of sleep disorders.

J Clin Sleep Med 2021 Mar;17(3):393-402

Center for Sleep Medicine and Respiratory Diseases, Croix-Rousse Hospital, Lyon, France.

Study Objectives: To assess the performance of the single-channel automatic sleep staging (AS) software ASEEGA in adult patients diagnosed with various sleep disorders.

Methods: Sleep recordings were included of 95 patients (38 women, 40.5 ± 13.7 years) diagnosed with insomnia (n = 23), idiopathic hypersomnia (n = 24), narcolepsy (n = 24), and obstructive sleep apnea (n = 24). Visual staging (VS) was performed by two experts (VS1 and VS2) according to the American Academy of Sleep Medicine rules. AS was based on the analysis of a single electroencephalogram channel (Cz-Pz), without any information from electro-oculography nor electromyography. The epoch-by-epoch agreement (concordance and Conger's coefficient [κ]) was compared pairwise (VS1-VS2, AS-VS1, AS-VS2) and between AS and consensual VS. Sleep parameters were also compared.

Results: The pairwise agreements were: between AS and VS1, 78.6% (κ = 0.70); AS and VS2, 75.0% (0.65); and VS1 and VS2, 79.5% (0.72). Agreement between AS and consensual VS was 85.6% (0.80), with the following distribution: insomnia 85.5% (0.80), narcolepsy 83.8% (0.78), idiopathic hypersomnia 86.1% (0.68), and obstructive sleep disorder 87.2% (0.82). A significant low-amplitude scorer effect was observed for most sleep parameters, not always driven by the same scorer. Hypnograms obtained with AS and VS exhibited very close sleep organization, except for 80% of rapid eye movement sleep onset in the group diagnosed with narcolepsy missed by AS.

Conclusions: Agreement between AS and VS in sleep disorders is comparable to that reported in healthy individuals and to interexpert agreement in patients. ASEEGA could therefore be considered as a complementary sleep stage scoring tool in clinical practice, after improvement of rapid eye movement sleep onset detection.
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http://dx.doi.org/10.5664/jcsm.8864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927318PMC
March 2021

Transient hypoxemia induced by cortical electrical stimulation: A mapping study in 75 patients.

Neurology 2020 06 5;94(22):e2323-e2336. Epub 2020 May 5.

From the Departments of Functional Neurology and Epileptology (M.L., J.J., S.R.) and Functional Neurosurgery (M.G.), Hospices Civils de Lyon and University of Lyon, France; Department of Clinical Neurosciences (P.R.), Centre Hospitalo-Universitaire Vaudois, Lausanne, Switzerland; INSERM U1028/CNRS UMR 5292 (B.C., J.J., R.B., M.G., L.M., L.B., S.R.), Lyon's Neuroscience Research Center; Neurology Department (L.M.), University Hospital, Saint-Etienne; and Epilepsy Institute (L.B., S.R.), Lyon, France.

Objective: To identify which cortical regions are associated with direct electrical stimulation (DES)-induced alteration of breathing significant enough to impair pulse oximetry (SpO).

Methods: Evolution of SpO after 1,352 DES was analyzed in 75 patients with refractory focal epilepsy who underwent stereo-EEG recordings. For each DES, we assessed the change in SpO from 30 seconds prior to DES onset to 120 seconds following the end of the DES. The primary outcome was occurrence of stimulation-induced transient hypoxemia as defined by decrease of SpO ≥5% within 60 seconds after stimulation onset as compared to pre-DES SpO or SpO nadir <90% during at least 5 seconds. Localization of the stimulated contacts was defined according to MarsAtlas brain parcellation and Freesurfer segmentation.

Results: A stimulation-induced transient hypoxemia was observed after 16 DES (1.2%) in 10 patients (13%), including 6 in whom SpO nadir was <90%. Among these 16 DES, 7 (44%) were localized within the perisylvian cortex. After correction for individual effects and the varying number of DES contributed by each person, significant decrease of SpO was significantly associated with the localization of DES ( = 0.019).

Conclusion: Though rare, a significant decrease of SpO could be elicited by cortical direct electrical stimulation outside the temporo-limbic structures, most commonly after stimulation of the perisylvian cortex.
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http://dx.doi.org/10.1212/WNL.0000000000009497DOI Listing
June 2020

Mindfulness meditation is related to sensory-affective uncoupling of pain in trained novice and expert practitioners.

Eur J Pain 2020 08 7;24(7):1301-1313. Epub 2020 May 7.

Lyon Neuroscience Research Centre, INSERM U1028, CNRS, UMR5292, Lyon 1 University, Bron Cedex, Lyon, France.

Background: Mindfulness meditation can alleviate acute and chronic pain. It has been proposed that mindfulness meditation reduces pain by uncoupling sensory and affective pain dimensions. However, studies to date have reported mixed results, possibly due to a diversity of styles of and expertise in mindfulness meditation. Furthermore, the interrelations between mindfulness meditation and pain catastrophizing during acute pain remain little known.

Methods: This cross-sectional study investigated the effect of a style of mindfulness meditation called Open Monitoring (OM) on sensory and affective pain experience by comparing novice (2-day formal training; average ~20 hr practice) to expert practitioners (>10.000 hr practice). We implemented a paradigm that was designed to amplify the cognitive-affective aspects of pain experience by the manipulation of pain anticipation and uncertainty of stimulus length (8 or 16 s thermal pain stimuli). We collected pain intensity and unpleasantness ratings and assessed trait pain catastrophizing with the Pain Catastrophizing Scale (PCS).

Results: Across groups, mindfulness meditation reduced unpleasantness, but not intensity ratings compared to attentional distraction. Experts reported a lower score on PCS, reduced amplification of unpleasantness by long painful stimuli, and larger sensory-affective uncoupling than novices particularly during long painful stimuli. In experts, meditation-induced uncoupling spilled over the control condition. Across groups and task conditions, a higher score on PCS predicted lower sensory-affective uncoupling during long painful stimuli and higher ratings of pain intensity during short painful stimuli.

Conclusion: These findings suggest that mindfulness meditation specifically down-regulates pain affect as opposed to pain intensity, and that pain catastrophizing undermines sensory-affective uncoupling of pain.

Significance: In this study, we found that a style of mindfulness meditation referred to as OM reduced unpleasantness but not intensity ratings compared to attentional distraction in trained novice (state effect) and expert meditators (state and trait effects). We also observed that trait pain catastrophizing scores predicted this sensory-affective uncoupling. These findings advance our understanding of the cognitive mechanisms underlying mindfulness meditation and can inform treatment strategies for chronic pain.
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http://dx.doi.org/10.1002/ejp.1576DOI Listing
August 2020

Exploring scoring methods for research studies: Accuracy and variability of visual and automated sleep scoring.

J Sleep Res 2020 10 18;29(5):e12994. Epub 2020 Feb 18.

GIGA-Cyclotron Research Centre-In vivo Imaging, University of Liège, Liège, Belgium.

Sleep studies face new challenges in terms of data, objectives and metrics. This requires reappraising the adequacy of existing analysis methods, including scoring methods. Visual and automatic sleep scoring of healthy individuals were compared in terms of reliability (i.e., accuracy and stability) to find a scoring method capable of giving access to the actual data variability without adding exogenous variability. A first dataset (DS1, four recordings) scored by six experts plus an autoscoring algorithm was used to characterize inter-scoring variability. A second dataset (DS2, 88 recordings) scored a few weeks later was used to explore intra-expert variability. Percentage agreements and Conger's kappa were derived from epoch-by-epoch comparisons on pairwise and consensus scorings. On DS1 the number of epochs of agreement decreased when the number of experts increased, ranging from 86% (pairwise) to 69% (all experts). Adding autoscoring to visual scorings changed the kappa value from 0.81 to 0.79. Agreement between expert consensus and autoscoring was 93%. On DS2 the hypothesis of intra-expert variability was supported by a systematic decrease in kappa scores between autoscoring used as reference and each single expert between datasets (.75-.70). Although visual scoring induces inter- and intra-expert variability, autoscoring methods can cope with intra-scorer variability, making them a sensible option to reduce exogenous variability and give access to the endogenous variability in the data.
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http://dx.doi.org/10.1111/jsr.12994DOI Listing
October 2020

Brain Volume Predicts Behavioral and Psychological Symptoms in Alzheimer's Disease.

J Alzheimers Dis 2020 ;73(4):1343-1353

Clinical and Research Memory Center of Lyon, Hospital of Charpennes, Lyon Institute for Elderly, University Hospital of Lyon, Lyon, France.

Background: Behavioral and psychological symptoms of dementia (BPSD) are frequent and troublesome for patients and caregivers. Considering possible preventive approaches, a better understanding of underlying neural correlates of BPSD is crucial.

Objective: The aim is to assess whether brain regional volume predicts behavioral changes in mild AD.

Methods: This work took part from the PACO study, a multicenter and prospective study that included 252 patients with mild AD from 2009 to 2014. Fifty-three patients were retained. Forty healthy matched control subjects from the ADNI cohort were included as controls. Voxel-based morphometry analysis was conducted to assess regional brain volume using baseline MRI scans as a predictor of future behavioral changes over a period of 18 months. Behavior was assessed at baseline and longitudinally at 6-month intervals using the shortened form of the Neuropsychiatric Inventory (NPI).

Results: The volume of 23 brain structures in frontal, temporal, parietal, occipital, subcortical regions and cerebellum predicted the evolution of NPI scores. Frontal volume was the most powerful predictor with frontal gyri, anterior cingulate cortex, and orbital gyri being particularly involved.

Conclusion: To our knowledge, this is the first study assessing regional brain volumes as predictors of behavioral changes considered at earlier stages of AD. Up to 23 brain structures were associated with an increased risk of developing BPSD. Frontal lobe volume was the strongest predictor of future evolution of NPI. The involvement of multiple structures in the prediction of behavior suggests a role of the main large-scale networks involved in cognition.
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http://dx.doi.org/10.3233/JAD-190612DOI Listing
May 2021

Regularized siamese neural network for unsupervised outlier detection on brain multiparametric magnetic resonance imaging: Application to epilepsy lesion screening.

Med Image Anal 2020 02 21;60:101618. Epub 2019 Nov 21.

Univ Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, F69621, Lyon, France. Electronic address:

In this study, we propose a novel anomaly detection model targeting subtle brain lesions in multiparametric MRI. To compensate for the lack of annotated data adequately sampling the heterogeneity of such pathologies, we cast this problem as an outlier detection problem and introduce a novel configuration of unsupervised deep siamese networks to learn normal brain representations using a series of non-pathological brain scans. The proposed siamese network, composed of stacked convolutional autoencoders as subnetworks is designed to map patches extracted from healthy control scans only and centered at the same spatial localization to 'close' representations with respect to the chosen metric in a latent space. It is based on a novel loss function combining a similarity term and a regularization term compensating for the lack of dissimilar pairs. These latent representations are then fed into oc-SVM models at voxel-level to produce anomaly score maps. We evaluate the performance of our brain anomaly detection model to detect subtle epilepsy lesions in multiparametric (T1-weighted, FLAIR) MRI exams considered as normal (MRI-negative). Our detection model trained on 75 healthy subjects and validated on 21 epilepsy patients (with 18 MRI-negatives) achieves a maximum sensitivity of 61% on the MRI-negative lesions, identified among the 5 most suspicious detections on average. It is shown to outperform detection models based on the same architecture but with stacked convolutional or Wasserstein autoencoders as unsupervised feature extraction mechanisms.
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http://dx.doi.org/10.1016/j.media.2019.101618DOI Listing
February 2020

BLAST paradigm: A new test to assess brief attentional fluctuations in children with epilepsy, ADHD, and normally developing children.

Epilepsy Behav 2019 10 17;99:106470. Epub 2019 Aug 17.

INSERM, U1028, CNRS, UMR5292, Lyon Neuroscience Research Center, Lyon, France; Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology, Member of the European Reference Network on Rare and Complex Epilepsies EpiCARE, Hospices Civils de Lyon and University Lyon, Lyon, France.

Background: Pure attentional deficits are still underdiagnosed in children with epilepsy. While attention-deficit hyperactivity disorder (ADHD) is historically the most studied cause of attentional disorders, an important number of children with epilepsy and attentional complaints do not fully meet the DSM-V (Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition) criteria for ADHD and may be excluded from specific care. Clinical tools currently available are insufficient to detect more subtle but clinically relevant attentional fluctuations.

Objective/methods: The recently developed Bron-Lyon Attention Stability Test (BLAST) was used to evaluate brief attentional fluctuations with a high temporal precision. Drawing on two new attentional indices, we evaluated spontaneous fluctuations of response accuracy and timing, underlying attentional stability. The main objective was to assess attentional stability in children with i) epilepsy with comorbid ADHD, ii) epilepsy without comorbid ADHD, iii) ADHD not medicated and without epilepsy, and iv) normal development. Further objectives were to assess the main determinants of attentional stability in those groups, including the effect of factors related to the epileptic condition.

Results: In 122 children with epilepsy (67 with comorbid ADHD), 52 children with ADHD, and 53 healthy controls, we demonstrated lower attentional stability in both the groups with epilepsy and ADHD compared with healthy children. In children with epilepsy, BLAST scores were negatively associated with earlier seizure onset and AED (antiepileptic drug) polytherapy, while the seizure frequency, epilepsy duration, or type did not influence BLAST scores.

Conclusions: This study demonstrates that attentional stability is impaired in children with epilepsy and/or ADHD. Bron-Lyon Attention Stability Test seems to be a sensitive test to detect attentional stability deficit in children with epilepsy and with attentional complaints who did not meet all criteria of ADHD. We propose that BLAST could be a useful clinical neuropsychological tool to assess attentional disorders in children.
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http://dx.doi.org/10.1016/j.yebeh.2019.106470DOI Listing
October 2019

Study protocol on Alzheimer's disease and related disorders: focus on clinical and imaging predictive markers in co-existing lesions.

BMC Geriatr 2018 11 14;18(1):280. Epub 2018 Nov 14.

Clinical and Research Memory Centre of Lyon, Hospital of Charpennes, Hospices Civils de Lyon, Lyon, France.

Background: One of the crucial challenges for the future of therapeutic approaches to Alzheimer's disease (AD) is to target the main pathological processes responsible for disability and dependency. However, a progressive cognitive impairment occurring after the age of 70, the main population affected by dementia, is often related to mixed lesions of neurodegenerative and vascular origins. Whereas young patients are mostly affected by pure lesions, ageing favours the occurrence of co-lesions of AD, cerebrovascular disease (CVD) and Lewy body dementia (LBD). Most of clinical studies report on functional and clinical disabilities in patients with presumed pure pathologies. But, the weight of co-morbid processes involved in the transition from an independent functional status to disability in the elderly with co-lesions still remains to be elucidated. Neuropathological examination often performed at late stages cannot answer this question at mild or moderate stages of cognitive disorders. Brain MRI, Single Photon Emission Computed Tomography (SPECT) with DaTscan®, amyloid Positron Emission Tomography (PET) and CerebroSpinal Fluid (CSF) AD biomarkers routinely help in performing the diagnosis of underlying lesions. The combination of these measures seems to be of incremental value for the diagnosis of mixed profiles of AD, CVD and LBD. The aim is to determine the clinical, neuropsychological, neuroradiological and biological features the most predictive of cognitive, behavioral and functional impairment at 2 years in patients with co-existing lesions.

Methods: A multicentre and prospective cohort study with clinical, neuro-imaging and biological markers assessment will recruit 214 patients over 70 years old with a cognitive disorder of AD, cerebrovascular and Lewy body type or with coexisting lesions of two or three of these pathologies and fulfilling the diagnostic criteria for dementia at a mild to moderate stage. Patients will be followed every 6 months (clinical, neuropsychological and imaging examination and collection of cognitive, behavioural and functional impairment) for 24 months.

Discussion: This study aims at identifying the best combination of markers (clinical, neuropsychological, MRI, SPECT-DaTscan®, PET and CSF) to predict disability progression in elderly patients presenting coexisting patterns.

Trial Registration: NCT02052947 .
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http://dx.doi.org/10.1186/s12877-018-0949-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236893PMC
November 2018

Saccadic Adaptation Boosts Ongoing Gamma Activity in a Subsequent Visuoattentional Task.

Cereb Cortex 2019 08;29(9):3606-3617

ImpAct Team, Lyon Neuroscience Research Center, INSERM U1028, CNRS-UMR5292, University Lyon1, 16, Ave. Doyen Lépine, France.

Attention and saccadic adaptation (SA) are critical components of visual perception, the former enhancing sensory processing of selected objects, the latter maintaining the eye movements accuracy toward them. Recent studies propelled the hypothesis of a tight functional coupling between these mechanisms, possibly due to shared neural substrates. Here, we used magnetoencephalography to investigate for the first time the neurophysiological bases of this coupling and of SA per se. We compared visual discrimination performance of 12 healthy subjects before and after SA. Eye movements and magnetic signals were recorded continuously. Analyses focused on gamma band activity (GBA) during the pretarget period of the discrimination and the saccadic tasks. We found that GBA increases after SA. This increase was found in the right hemisphere for both postadaptation saccadic and discrimination tasks. For the latter, GBA also increased in the left hemisphere. We conclude that oculomotor plasticity involves GBA modulation within an extended neural network which persists after SA, suggesting a possible role of gamma oscillations in the coupling between SA and attention.
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http://dx.doi.org/10.1093/cercor/bhy241DOI Listing
August 2019

Two Sides of the Same Coin: Distinct Sub-Bands in the α Rhythm Reflect Facilitation and Suppression Mechanisms during Auditory Anticipatory Attention.

eNeuro 2018 Jul-Aug;5(4). Epub 2018 Sep 17.

Brain Dynamics and Cognition Team, Lyon Neuroscience Research Center; CRNL, Institut National de la Santé et de la Recherche Médicale Unité 1028, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5292, Université de Lyon, Lyon, France 69500.

Anticipatory attention results in enhanced response to task-relevant stimulus, and reduced processing of unattended input, suggesting the deployment of distinct facilitatory and suppressive mechanisms. α Oscillations are a suitable candidate for supporting these mechanisms. We aimed to examine the role of α oscillations, with a special focus on peak frequencies, in facilitatory and suppressive mechanisms during auditory anticipation, within the auditory and visual regions. Magnetoencephalographic (MEG) data were collected from fourteen healthy young human adults (eight female) performing an auditory task in which spatial attention to sounds was manipulated by visual cues, either informative or not of the target side. By incorporating uninformative cues, we could delineate facilitating and suppressive mechanisms. During anticipation of a visually-cued auditory target, we observed a decrease in α power around 9 Hz in the auditory cortices; and an increase around 13 Hz in the visual regions. Only this power increase in high α significantly correlated with behavior. Importantly, within the right auditory cortex, we showed a larger increase in high α power when attending an ipsilateral sound; and a stronger decrease in low α power when attending a contralateral sound. In summary, we found facilitatory and suppressive attentional mechanisms with distinct timing in task-relevant and task-irrelevant brain areas, differentially correlated to behavior and supported by distinct α sub-bands. We provide new insight into the role of the α peak-frequency by showing that anticipatory attention is supported by distinct facilitatory and suppressive mechanisms, mediated in different low and high sub-bands of the α rhythm, respectively.
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http://dx.doi.org/10.1523/ENEURO.0141-18.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140117PMC
February 2019

Task-induced gamma band effect in type II focal cortical dysplasia: An exploratory study.

Epilepsy Behav 2018 08 14;85:76-84. Epub 2018 Jun 14.

Department of Functional Neurology and Epileptology, Hospices civils de Lyon, Lyon, France; Lyon 1 University, Lyon, France; Lyon's Neuroscience Research Center, INSERM U1028, CNRS UMR 5292, Lyon, France. Electronic address:

Objective: Few data are available about the functionality of type II focal cortical dysplasia (FCD). Identification of high-frequency activities (HFAs) induced by cognitive tasks has been proposed as an additional way to map cognitive functions in patients undergoing presurgical evaluation using stereoelectroencephalography (SEEG). However, the repetitive subcontinuous spiking pattern which characterizes type II FCD might limit the reliability of this approach, and its feasibility in these patients remains to be evaluated.

Methods: Seven patients whose magnetic resonance imaging (MRI) data, SEEG data, and/or pathological data were consistent with the diagnosis of type II FCD were included. All patients performed standardized cognitive tasks specifically designed to map task-induced increase of HFA (50 Hz to 150 Hz) at the recorded sites. Electrode contacts which showed an interictal SEEG pattern typical of type II FCD were considered to be localized within the FCD. A site was considered responsive if it was significantly different from baseline in at least one cognitive task.

Results: Three of the seven patients (43%) had significant task-induced increase of HFA in the FCD for a total of 15 sites with an interictal SEEG pattern typical of type II FCD. These sites were always localized at the external border of the FCD whereas no HFA response was in the core of FCD. In three of the four other patients, a significant task-induced increase of HFA was observed in a cortical site immediately adjacent to the dysplastic cortex.

Significance: Detection of task-induced HFA remains feasible despite the repetitive subcontinuous spiking pattern which characterizes type II FCD. Depending on the localization of the FCD, some sites of the dysplastic cortex were included in large-scale functional networks. However, these sites were always those closest to the nondysplastic cortex suggesting that persistence of cortical functions might be restricted to a limited part of the FCD.
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http://dx.doi.org/10.1016/j.yebeh.2018.05.017DOI Listing
August 2018

Long-interval intracortical inhibition as biomarker for epilepsy: a transcranial magnetic stimulation study.

Brain 2018 02;141(2):409-421

NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.

Cortical excitability, as measured by transcranial magnetic stimulation combined with electromyography, is a potential biomarker for the diagnosis and follow-up of epilepsy. We report on long-interval intracortical inhibition data measured in four different centres in healthy controls (n = 95), subjects with refractory genetic generalized epilepsy (n = 40) and with refractory focal epilepsy (n = 69). Long-interval intracortical inhibition was measured by applying two supra-threshold stimuli with an interstimulus interval of 50, 100, 150, 200 and 250 ms and calculating the ratio between the response to the second (test stimulus) and to the first (conditioning stimulus). In all subjects, the median response ratio showed inhibition at all interstimulus intervals. Using a mixed linear-effects model, we compared the long-interval intracortical inhibition response ratios between the different subject types. We conducted two analyses; one including data from the four centres and one excluding data from Centre 2, as the methods in this centre differed from the others. In the first analysis, we found no differences in long-interval intracortical inhibition between the different subject types. In all subjects, the response ratios at interstimulus intervals 100 and 150 ms showed significantly more inhibition than the response ratios at 50, 200 and 250 ms. Our second analysis showed a significant interaction between interstimulus interval and subject type (P = 0.0003). Post hoc testing showed significant differences between controls and refractory focal epilepsy at interstimulus intervals of 100 ms (P = 0.02) and 200 ms (P = 0.04). There were no significant differences between controls and refractory generalized epilepsy groups or between the refractory generalized and focal epilepsy groups. Our results do not support the body of previous work that suggests that long-interval intracortical inhibition is significantly reduced in refractory focal and genetic generalized epilepsy. Results from the second analysis are even in sharper contrast with previous work, showing inhibition in refractory focal epilepsy at 200 ms instead of facilitation previously reported. Methodological differences, especially shorter intervals between the pulse pairs, may have contributed to our inability to reproduce previous findings. Based on our results, we suggest that long-interval intracortical inhibition as measured by transcranial magnetic stimulation and electromyography is unlikely to have clinical use as a biomarker of epilepsy.
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http://dx.doi.org/10.1093/brain/awx343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837684PMC
February 2018

The neural bases of ictal tachycardia in temporal lobe seizures.

Clin Neurophysiol 2017 09 27;128(9):1810-1819. Epub 2017 Jun 27.

Dycog Lab, Lyon Neuroscience Research Center - Inserm U 1028/CNRS UMR 5292, University of Lyon, France; Epilepsy and Functional Neurology Department, Neurological Hospital Pierre Wertheimer, Hospices Civils de Lyon, Bron, France.

Objective: Due to limited information from scalp electroencephalographic (EEG) recordings, brain areas driving changes in cardiac rhythm during Temporal lobe (TL) seizures are not clearly identified. Using stereotactic EEG (SEEG) recordings, we aimed at identifying which of the brain regions involved in autonomic control trigger ictal tachycardia.

Methods: The neural activity of several mesial temporal lobe structures including amygdala, hippocampus, insula, and lateral temporal lobe recorded with SEEG were collected during 37 TL seizures in 9 patients, using indices based on High Frequency Activity (HFA). R-R intervals (RR) monitoring and time-frequency spectral analysis were performed to assess parasympathetic (High frequency power (HF)) and sympathetic (Low frequency/High frequency (LF/HF) ratio) reactivities.

Results: Tachycardia was associated with a significant increase in LF/HF ratio and decrease in HF. Autonomic cardiac changes were accompanied by simultaneous SEEG signal changes with an increase in seizure-related HFA in anterior hippocampal formation and amygdala, but not in insula.

Conclusion: In our sample, TL seizures are thus accompanied by an early decrease in parasympathetic control of cardiac rhythm and by an increase of sympathetic tone, concomitant to seizure activity in anterior hippocampus and amygdala.

Significance: These results support a pivotal role of hippocampus and amygdala in tachycardia occurring during TL seizures.
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http://dx.doi.org/10.1016/j.clinph.2017.06.033DOI Listing
September 2017

The relationship between morphological lesion, magnetic source imaging, and intracranial stereo-electroencephalography in focal cortical dysplasia.

Neuroimage Clin 2017 20;15:71-79. Epub 2017 Apr 20.

Lyon Neuroscience Research Center, INSERM U1028, CNRS UMR5292, Brain Dynamics and Cognition Team, Lyon F-69000, France; Université Lyon 1, Lyon F-69000, France; Hospices Civils de Lyon, Neurological Hospital, Functional Neurology and Epileptology Dept, Lyon F-69003, France. Electronic address:

Magnetoencephalography (MEG) is a useful non-invasive technique for presurgical evaluation of focal cortical dysplasia patients. We aimed at clarifying the precise spatial relationship between the spiking volume determined with MEG, the seizure onset zone and the lesional volume in patients with focal cortical dysplasia. We studied the spatial relationships between the MEG spiking volume determined with a recent analysis pipeline, the seizure-onset zone location determined with a quantitative index calculated from intracranial EEG signals ('Epileptogenicity Index') and the lesional volume delineated on brain MRI in 11 patients with Focal Cortical Dysplasia explored with Stereo-electroencephalography (SEEG). A significant correlation between the MEG spiking activity and the Epileptogenicity Index was found in 8/11 patients. 7/8 patients were operated upon and had good surgical outcome. For three patients, no correlation between Epileptogenicity Index and spiking activity was observed; only one of those three patients had good surgical outcome. The lesion was at least partially overlapping with the seizure-onset zone in 8/9 patients with a lesion clearly identifiable by MRI. However, 57% of the SEEG epileptogenic contacts were located outside of the lesional volume. Lastly 44% of the highly epileptogenic SEEG contacts were located within the spiking volume and 22% of them were located exclusively in the spiking volume and not in the lesion. For 7/9 patients with a lesion, < 50% of epileptogenic SEEG contacts were included within the lesion: for 5/7 patients MEG provided an added value for targeting the epileptogenic region through intracranial electrodes, while for two of seven patients MEG detected only a few extralesional epileptogenic contacts. Our study suggests that modeling of the spiking volume with MEG is a promising tool to localize non-invasively the seizure-onset zone in patients with focal cortical dysplasia. Combined with brain MRI, MEG modeling of the spiking volume contributes to delineate the spatial extent of the seizure-onset zone.
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http://dx.doi.org/10.1016/j.nicl.2017.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412109PMC
March 2018

How can we explain the frontal presentation of insular lobe epilepsy? The impact of non-linear analysis of insular seizures.

Clin Neurophysiol 2017 05 13;128(5):780-791. Epub 2017 Feb 13.

Université Lyon 1, Lyon F-69000, France; Hospices Civils de Lyon, Neurological Hospital, Department of Functional Neurology and Epileptology, Lyon F-69003, France; Central Integration of Pain (NeuroPain) Lab-Lyon Neuroscience Research Center, INSERM U1028, CNRS, UMR5292, Université Claude Bernard, Bron F-69677, France.

Objective: For a decade it has been known that the insular lobe epilepsy can mimic frontal lobe epilepsy. We aimed to clarify the pattern of functional coupling occurring during the frontal presentation.

Methods: We analyzed five insular lobe epilepsy patients. Frontal semiology was predominant for three of them, whereas insular semiology was predominant for the two others. We applied the non-linear regression analysis to stereoelectroencephalography-recorded seizures. A directed functional coupling index was calculated during clonic discharge periods that were accompanied either with frontal or insular semiology.

Results: We found significant functional coupling between the insula and mesial frontal/cingulate regions, with the former being a leader region for seizures propagation. Extra-insular regions showed significantly less or even no coupling with the mesial hemispheric regions. The three patients with frontal semiology showed strong couplings with the mesial frontal as well as cingulate regions, including the medial orbitofrontal cortex, pre-SMA/SMA, and the anterior to posterior cingulate. The two patients with the insular semiology only showed couplings between the insula and cingulate regions.

Conclusions: The frontal semiology was expressed by strong functional couplings between the insula and mesial frontal regions.

Significance: The insular origin of seizure should be considered in cryptogenic mesial frontal epilepsies.
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http://dx.doi.org/10.1016/j.clinph.2017.01.022DOI Listing
May 2017

Neural Activity Elicited by a Cognitive Task can be Detected in Single-Trials with Simultaneous Intracerebral EEG-fMRI Recordings.

Int J Neural Syst 2017 Feb 22;27(1):1750001. Epub 2016 Aug 22.

† Epilepsy Institute IDEE, Lyon, France.

Recent studies have shown that it is feasible to record simultaneously intracerebral EEG (icEEG) and functional magnetic resonance imaging (fMRI) in patients with epilepsy. While it has mainly been used to explore the hemodynamic changes associated with epileptic spikes, this approach could also provide new insight into human cognition. However, the first step is to ensure that cognitive EEG components, that have lower amplitudes than epileptic spikes, can be appropriately detected under fMRI. We compared the high frequency activities (HFA, 50-150[Formula: see text]Hz) elicited by a reading task in icEEG-only and subsequent icEEG-fMRI in the same patients ([Formula: see text]), implanted with depth electrodes. Comparable responses were obtained, with 71% of the recording sites that responded during the icEEG-only session also responding during the icEEG-fMRI session. For all the remaining sites, nearby clusters (distant of 7[Formula: see text]mm or less) also demonstrated significant HFA increase during the icEEG-fMRI session. Significant HFA increases were also observable at the single-trial level in icEEG-fMRI recordings. Our results show that low-amplitude icEEG signal components such as cognitive-induced HFAs can be reliably recorded with simultaneous fMRI. This paves the way for the use of icEEG-fMRI to address various fundamental and clinical issues, notably the identification of the neural correlates of the BOLD signal.
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http://dx.doi.org/10.1142/S0129065717500010DOI Listing
February 2017

Detection of Lesions Underlying Intractable Epilepsy on T1-Weighted MRI as an Outlier Detection Problem.

PLoS One 2016 7;11(9):e0161498. Epub 2016 Sep 7.

Université de Lyon, CREATIS; CNRS UMR5220; INSERM U1206; INSA-Lyon; Univ. Lyon 1, France.

Pattern recognition methods, such as computer aided diagnosis (CAD) systems, can help clinicians in their diagnosis by marking abnormal regions in an image. We propose a machine learning system based on a one-class support vector machine (OC-SVM) classifier for the detection of abnormalities in magnetic resonance images (MRI) applied to patients with intractable epilepsy. The system learns the features associated with healthy control subjects, allowing a voxelwise assessment of the deviation of a test subject pattern from the learned patterns. While any number of various features can be chosen and learned, here we focus on two texture parameters capturing image patterns associated with epileptogenic lesions on T1-weighted brain MRI e.g. heterotopia and blurred junction between the grey and white matter. The CAD output consists of patient specific 3D maps locating clusters of suspicious voxels ranked by size and degree of deviation from control patterns. System performance was evaluated using realistic simulations of challenging detection tasks as well as clinical data of 77 healthy control subjects and of eleven patients (13 lesions). It was compared to that of a mass univariate statistical parametric mapping (SPM) single subject analysis based on the same set of features. For all simulations, OC-SVM yielded significantly higher values of the area under the ROC curve (AUC) and higher sensitivity at low false positive rate. For the clinical data, both OC-SVM and SPM successfully detected 100% of the lesions in the MRI positive cases (3/13). For the MRI negative cases (10/13), OC-SVM detected 7/10 lesions and SPM analysis detected 5/10 lesions. In all experiments, OC-SVM produced fewer false positive detections than SPM. OC-SVM may be a versatile system for unbiased lesion detection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161498PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015774PMC
August 2017

Gamma oscillations in V1 are correlated with GABA(A) receptor density: A multi-modal MEG and Flumazenil-PET study.

Sci Rep 2015 Nov 17;5:16347. Epub 2015 Nov 17.

Lyon Neuroscience Research Center, INSERM U1028-CNRS UMR5292, F-69000, Lyon, France.

High-frequency oscillations in the gamma-band reflect rhythmic synchronization of spike timing in active neural networks. The modulation of gamma oscillations is a widely established mechanism in a variety of neurobiological processes, yet its neurochemical basis is not fully understood. Modeling, in-vitro and in-vivo animal studies suggest that gamma oscillation properties depend on GABAergic inhibition. In humans, search for evidence linking total GABA concentration to gamma oscillations has led to promising -but also to partly diverging- observations. Here, we provide the first evidence of a direct relationship between the density of GABA(A) receptors and gamma oscillatory gamma responses in human primary visual cortex (V1). By combining Flumazenil-PET (to measure resting-levels of GABA(A) receptor density) and MEG (to measure visually-induced gamma oscillations), we found that GABA(A) receptor densities correlated positively with the frequency and negatively with amplitude of visually-induced gamma oscillations in V1. Our findings demonstrate that gamma-band response profiles of primary visual cortex across healthy individuals are shaped by GABA(A)-receptor-mediated inhibitory neurotransmission. These results bridge the gap with in-vitro and animal studies and may have future clinical implications given that altered GABAergic function, including dysregulation of GABA(A) receptors, has been related to psychiatric disorders including schizophrenia and depression.
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http://dx.doi.org/10.1038/srep16347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647220PMC
November 2015

The value of magnetoencephalography for seizure-onset zone localization in magnetic resonance imaging-negative partial epilepsy.

Brain 2013 Oct 6;136(Pt 10):3176-86. Epub 2013 Sep 6.

1 Lyon Neuroscience Research Centre, INSERM U1028, CNRS UMR5292, Brain Dynamics and Cognition Team, Lyon, F-69000, France.

Surgical treatment of epilepsy is a challenge for patients with non-contributive brain magnetic resonance imaging. However, surgery is feasible if the seizure-onset zone is precisely delineated through intracranial electroencephalography recording. We recently described a method, volumetric imaging of epileptic spikes, to delineate the spiking volume of patients with focal epilepsy using magnetoencephalography. We postulated that the extent of the spiking volume delineated with volumetric imaging of epileptic spikes could predict the localizability of the seizure-onset zone by intracranial electroencephalography investigation and outcome of surgical treatment. Twenty-one patients with non-contributive magnetic resonance imaging findings were included. All patients underwent intracerebral electroencephalography investigation through stereotactically implanted depth electrodes (stereo-electroencephalography) and magnetoencephalography with delineation of the spiking volume using volumetric imaging of epileptic spikes. We evaluated the spatial congruence between the spiking volume determined by magnetoencephalography and the localization of the seizure-onset zone determined by stereo-electroencephalography. We also evaluated the outcome of stereo-electroencephalography and surgical treatment according to the extent of the spiking volume (focal, lateralized but non-focal or non-lateralized). For all patients, we found a spatial overlap between the seizure-onset zone and the spiking volume. For patients with a focal spiking volume, the seizure-onset zone defined by stereo-electroencephalography was clearly localized in all cases and most patients (6/7, 86%) had a good surgical outcome. Conversely, stereo-electroencephalography failed to delineate a seizure-onset zone in 57% of patients with a lateralized spiking volume, and in the two patients with bilateral spiking volume. Four of the 12 patients with non-focal spiking volumes were operated upon, none became seizure-free. As a whole, patients having focal magnetoencephalography results with volumetric imaging of epileptic spikes are good surgical candidates and the implantation strategy should incorporate volumetric imaging of epileptic spikes results. On the contrary, patients with non-focal magnetoencephalography results are less likely to have a localized seizure-onset zone and stereo electroencephalography is not advised unless clear localizing information is provided by other presurgical investigation methods.
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http://dx.doi.org/10.1093/brain/awt213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784280PMC
October 2013

Impaired pitch perception and memory in congenital amusia: the deficit starts in the auditory cortex.

Brain 2013 May;136(Pt 5):1639-61

INSERM U1028-CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, Equipe Dynamique Cérébrale et Cognition, Centre Hospitalier le Vinatier, Batiment 452, 95 Bd Pinel, Bron, F-69500, France.

Congenital amusia is a lifelong disorder of music perception and production. The present study investigated the cerebral bases of impaired pitch perception and memory in congenital amusia using behavioural measures, magnetoencephalography and voxel-based morphometry. Congenital amusics and matched control subjects performed two melodic tasks (a melodic contour task and an easier transposition task); they had to indicate whether sequences of six tones (presented in pairs) were the same or different. Behavioural data indicated that in comparison with control participants, amusics' short-term memory was impaired for the melodic contour task, but not for the transposition task. The major finding was that pitch processing and short-term memory deficits can be traced down to amusics' early brain responses during encoding of the melodic information. Temporal and frontal generators of the N100m evoked by each note of the melody were abnormally recruited in the amusic brain. Dynamic causal modelling of the N100m further revealed decreased intrinsic connectivity in both auditory cortices, increased lateral connectivity between auditory cortices as well as a decreased right fronto-temporal backward connectivity in amusics relative to control subjects. Abnormal functioning of this fronto-temporal network was also shown during the retention interval and the retrieval of melodic information. In particular, induced gamma oscillations in right frontal areas were decreased in amusics during the retention interval. Using voxel-based morphometry, we confirmed morphological brain anomalies in terms of white and grey matter concentration in the right inferior frontal gyrus and the right superior temporal gyrus in the amusic brain. The convergence between functional and structural brain differences strengthens the hypothesis of abnormalities in the fronto-temporal pathway of the amusic brain. Our data provide first evidence of altered functioning of the auditory cortices during pitch perception and memory in congenital amusia. They further support the hypothesis that in neurodevelopmental disorders impacting high-level functions (here musical abilities), abnormalities in cerebral processing can be observed in early brain responses.
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http://dx.doi.org/10.1093/brain/awt082DOI Listing
May 2013

Towards source volume estimation of interictal spikes in focal epilepsy using magnetoencephalography.

Neuroimage 2012 Feb 21;59(4):3955-66. Epub 2011 Oct 21.

Lyon Neuroscience Research Center, INSERM U1028, CNRS UMR5292, Brain Dynamics and Cognition Team, Lyon F-69000, France.

Interictal spikes are a hallmark of cortical epileptogenicity; their spatial distribution in the cortex defines the so-called 'irritative' zone or spiking volume (SV). Delineating the SV precisely is a challenge during the presurgical evaluation of patients with epilepsy. Magnetoencephalography (MEG) recordings enable determination of the brain sources of epileptic spikes using source localization procedures. Most previous clinical MEG studies have relied on dipole modeling of epileptic spikes, which does not permit a volumetric estimation of the spiking cortex. In the present study, we propose a new source modeling procedure, Volumetric Imaging of Epileptic Spikes (VIES). In VIES, the SV is identified as the 3D region where sources of the high frequency activities (>20 Hz) associated with epileptic spikes are distributed. We localized these sources using a beamforming approach (DICS, Dynamic Imaging of Coherent Neural Sources). To determine the optimal parameters and accuracy of the method, we compared the SV obtained by VIES with the SV defined by the invasive gold standard, intracranial stereotactic EEG recordings (SEEG), in 21 patients with focal epilepsy. Using rigorous validation criteria based on the exact anatomical location of SEEG contacts, we found that the overall sensitivity of VIES for detecting spiking SEEG contacts was 76% and its specificity for correctly identifying non-spiking SEEG contacts was 67%, indicating a good agreement between VIES and SEEG. Moreover, we found that classical dipole clustering was not informative in 9/21 patients, while VIES enable to delineate the SV in all patients. For the 12 patients having a SV delineated both with VIES and dipole clustering, VIES method had higher sensitivity and lower specificity. This proof-of-concept study shows that VIES is a promising approach to non-invasive estimation of the SV in focal epilepsy.
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http://dx.doi.org/10.1016/j.neuroimage.2011.10.052DOI Listing
February 2012

Perceptual classification of chromatic modulation.

Vis Neurosci 2004 May-Jun;21(3):283-9

Institut National de la Santé et de la Recherche Médicale, Cerveau et Vision, Bron cedex, France.

We measured the regions of the equiluminant plane that are exploited by observers during a Yes/No detection task. The signal was a 640-ms Gaussian modulation (sigma(t) = 160 ms) of a Gaussian spatial patch (sigma(s) = 2.4 deg) presented in chromatically bivariate uniform noise. One component of the noise was along the direction axial with the signal in color space, the other perpendicular. Four signal directions were tested: along cardinal LM and S axes and two intermediate directions to which the cardinal axes were equally sensitive. The distribution of noise chromaticities from each trial was correlated with the observers' responses and the presence and absence of the signal to build a classification image of the distribution of chromaticities on which the decision of the observer was based. The images show a narrowly selective peak in the signal direction flanked by regions with a broader selectivity. These results raise the possibility that detection judgments are mediated by both linear and nonlinear mechanisms with peak sensitivities between the cardinal directions.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1913556PMC
http://dx.doi.org/10.1017/s0952523804213141DOI Listing
January 2005