Bayesian multi-modal model comparison: a case study on the generators of the spike and the wave in generalized spike–wave complexes

We present a novel approach to assess the networks involved in the generation of spontaneous pathological brain activity based on multi-modal imaging data. We propose to use probabilistic fMRI-constrained EEG source reconstruction as a complement to EEG-correlated fMRI analysis to disambiguate between networks that co-occur at the fMRI time resolution. The method is based on Bayesian model comparison, where the different models correspond to different combinations of fMRI-activated (or deactivated) cortical clusters. By computing the model evidence (or marginal likelihood) of each and every candidate source space partition, we can infer the most probable set of fMRI regions that has generated a given EEG scalp data window. We illustrate the method using EEG-correlated fMRI data acquired in a patient with ictal generalized spike–wave (GSW) discharges, to examine whether different networks are involved in the generation of the spike and the wave components, respectively. To this effect, we compared a family of 128 EEG source models, based on the combinations of seven regions haemodynamically involved (deactivated) during a prolonged ictal GSW discharge, namely: bilateral precuneus, bilateral medial frontal gyrus, bilateral middle temporal gyrus, and right cuneus. Bayesian model comparison has revealed the most likely model associated with the spike component to consist of a prefrontal region and bilateral temporal–parietal regions and the most likely model associated with the wave component to comprise the same temporal–parietal regions only. The result supports the hypothesis of different neurophysiological mechanisms underlying the generation of the spike versus wave components of GSW discharges

Mapping the Effect of Interictal Epileptic Activity Density During Wakefulness on Brain Functioning in Focal Childhood Epilepsies With Centrotemporal Spikes

Childhood epilepsy with centrotemporal spikes (CECTS) is the most common type of \u201cself-limited focal epilepsies.\u201d In its typical presentation, CECTS is a condition reflecting non-lesional cortical hyperexcitability of rolandic regions. The benign evolution of this disorder is challenged by the frequent observation of associated neuropsychological deficits and behavioral impairment. The abundance (or frequency) of interictal centrotemporal spikes (CTS) in CECTS is considered a risk factor for deficits in cognition. Herein, we captured the hemodynamic changes triggered by the CTS density measure (i.e., the number of CTS for time bin) obtained in a cohort of CECTS, studied by means of video electroencephalophy/functional MRI during quite wakefulness. We aim to demonstrate a direct influence of the diurnal CTS frequency on epileptogenic and cognitive networks of children with CECTS. A total number of 8,950 CTS (range between 27 and 801) were recorded in 23 CECTS (21 male), with a mean number of 255 CTS/patient and a mean density of CTS/30 s equal to 10,866 \ub1 11.46. Two independent general linear model models were created for each patient based on the effect of interest: \u201cindividual CTS\u201d in model 1 and \u201cCTS density\u201d in model 2. Hemodynamic correlates of CTS density revealed the involvement of a widespread cortical\u2013subcortical network encompassing the sensory-motor cortex, the Broca's area, the premotor cortex, the thalamus, the putamen, and red nucleus, while in the CTS event-related model, changes were limited to blood\u2013oxygen-level-dependent (BOLD) signal increases in the sensory-motor cortices. A linear relationship was observed between the CTS density hemodynamic changes and both disease duration (positive correlation) and age (negative correlation) within the language network and the bilateral insular cortices. Our results strongly support the critical role of the CTS frequency, even during wakefulness, to interfere with the normal functioning of language brain networks

The neuronal network of laughing in young patients with untreated narcolepsy

Objective To investigate the neuronal correlates of spontaneous laughter in drug-naive pediatric patients with narcolepsy type I (NT1) compared to healthy controls by means of blood oxygen leveldependent (BOLD) MRI. Methods Twenty-one children/adolescents with recent onset of NT1 and 21 age- and sex-matched healthy controls were studied with fMRI while viewing funny videos using a naturalistic paradigm. Whole-brain hemodynamic correlates of spontaneous laughter were investigated in each group and compared by use of appropriate second-level general linear model analyses. If recorded, cataplexy events were treated as the effect of no interest at the single-participant level. Correlations analyses between these contrasts and behavioral findings were performed. Results Emotion-induced laughter occurred in 16 patients (294 events) and 21 controls (357 events). In controls, laughter-related BOLD increases involved a widespread cortical and subcortical network including the bilateral motor and premotor areas, cingulated cortex, insula, and amygdala. In NT1, laughter induced BOLD signal increments in the motor cortex, right thalamus, and left subthalamic nucleus/zona incerta (STN/ZI). STN/ZI and thalamic changes were significantly higher during fMRI sessions with laughter without cataplexy compared to sessions in which laughter was associated with cataplexy. Conclusion Laughter expression in individuals with NT1 involves different brain circuits compared to controls by means of overactivation of cortical and subcortical regions belonging to the volitional control of laughter. The activation of the STN/ZI region observed predominantly in patients with NT1 during laugh episodes without cataplexy suggests that the ZI could act to prevent cataplexy

The effect of chronic neuroglycopenia on resting state networks in GLUT1 syndrome across the lifespan

Glucose transporter type I deficiency syndrome (GLUT1DS) is an encephalopathic disorder due to a chronic insufficient transport of glucose into the brain. PET studies in GLUT1DS documented a widespread cortico-thalamic hypometabolism and a signal increase in the basal ganglia, regardless of age and clinical phenotype. Herein, we captured the pattern of functional connectivity of distinct striatal, cortical, and cerebellar regions in GLUT1DS (10 children, eight adults) and in healthy controls (HC, 19 children, 17 adults) during rest. Additionally, we explored for regional connectivity differences in GLUT1 children versus adults and according to the clinical presentation. Compared to HC, GLUT1DS exhibited increase connectivity within the basal ganglia circuitries and between the striatal regions with the frontal cortex and cerebellum. The excessive connectivity was predominant in patients with movement disorders and in children compared to adults, suggesting a correlation with the clinical phenotype and age at fMRI study. Our findings highlight the primary role of the striatum in the GLUT1DS pathophysiology and confirm the dependency of symptoms to the patients' chronological age. Despite the reduced chronic glucose uptake, GLUT1DS exhibit increased connectivity changes in regions highly sensible to glycopenia. Our results may portrait the effect of neuroprotective brain strategy to overcome the chronic poor energy supply during vulnerable ages

Association Between Particular Foetal Malformations and Antiepileptic Drug Exposure

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Recommendations for the use of structural magnetic resonance imaging in the care of patients with epilepsy: A consensus report from the International League Against Epilepsy Neuroimaging Task Force.

Structural magnetic resonance imaging (MRI) is of fundamental importance to the diagnosis and treatment of epilepsy, particularly when surgery is being considered. Despite previous recommendations and guidelines, practices for the use of MRI are variable worldwide and may not harness the full potential of recent technological advances for the benefit of people with epilepsy. The International League Against Epilepsy Diagnostic Methods Commission has thus charged the 2013-2017 Neuroimaging Task Force to develop a set of recommendations addressing the following questions: (1) Who should have an MRI? (2) What are the minimum requirements for an MRI epilepsy protocol? (3) How should magnetic resonance (MR) images be evaluated? (4) How to optimize lesion detection? These recommendations target clinicians in established epilepsy centers and neurologists in general/district hospitals. They endorse routine structural imaging in new onset generalized and focal epilepsy alike and describe the range of situations when detailed assessment is indicated. The Neuroimaging Task Force identified a set of sequences, with three-dimensional acquisitions at its core, the harmonized neuroimaging of epilepsy structural sequences-HARNESS-MRI protocol. As these sequences are available on most MR scanners, the HARNESS-MRI protocol is generalizable, regardless of the clinical setting and country. The Neuroimaging Task Force also endorses the use of computer-aided image postprocessing methods to provide an objective account of an individual's brain anatomy and pathology. By discussing the breadth and depth of scope of MRI, this report emphasizes the unique role of this noninvasive investigation in the care of people with epilepsy

Epilepsy-related brain networks in ring chromosome 20 syndrome : an EEG-fMRI study

Objective To identify the brain networks that are involved in the different electroencephalography (EEG) abnormalities in patients with ring chromosome 20 [r(20)] syndrome. We hypothesize the existence of both distinctive and common brain circuits for the paroxysmal high voltage sharp waves (hSWs), the seizures, and the slow-wave 3\u20137 Hz rhythm that characterize this condition. Methods Thirteen patients with [r(20)] syndrome were studied by means of EEG simultaneously recorded with functional magnetic resonance imaging (EEG-fMRI). EEG traces were reviewed in order to detect the pathologic interictal (hSWs) and ictal activities; the 3\u20137 Hz theta-delta power was derived using a fast Fourier transform. A group-level analysis was performed for each type of EEG abnormality separately using a fixed-effect model and a conjunction analysis. Finally, a second-level random-effect model was applied considering together the different EEG abnormalities, without distinction between hSW, seizures, or theta-delta rhythms. Results Subcontinuous theta-delta rhythm was recorded in seven patients, seizures in two, and hSWs in three patients. The main results are the following: (1) the slow-wave rhythm was related to blood oxygen level\u2013dependent (BOLD) increases in the premotor, sensory-motor, and temporoparietal cortex, and to BOLD decrements involving the default mode (DMN) and the dorsal attention networks (DANs); (2) the ictal-related BOLD changes showed an early involvement of the prefrontal lobe; (3) increases in BOLD signal over the basal ganglia, either for interictal and ictal activities, were observed; (4) a common pattern of positive BOLD changes in the bilateral perisylvian regions was found across the different EEG abnormalities. Significance The BOLD increment in the perisylvian network and the decrease of the DMN and DAN could be the expression of the [r(20)] syndrome\u2013related cognitive and behavioral deficits. The observed BOLD patterns are similar to the ones detected in other epileptic encephalopathies, suggesting that different epileptic disorders characterized by neurobehavioral regression are associated with dysfunction in similar brain networks

The visual system in eyelid myoclonia with absences

Objective: To investigate the functional and structural brain correlates of eyelid myoclonus and absence seizures triggered by eye closure (eye closure sensitivity [ECS]). Methods: Fifteen patients with eyelid myoclonus with absences (EMA, Jeavons syndrome), 14 patients with idiopathic generalized epilepsies (IGE) without ECS, and 16 healthy controls (HC) underwent an electroencephalography (EEG)-correlated functional magnetic resonance imaging (fMRI) and voxel brain morphometry (VBM) protocol. The functional study consisted of 30-second epochs of eyes-open and eyes-closed conditions. The following EEG events were marked and the relative fMRI maps obtained: (1) eye closure times, (2) spontaneous blinking, and (3) spontaneous and eye closure-triggered spike and wave discharges (SWD; for EMA and IGE). Within-group and betweengroups comparisons were performed for fMRI and VBM data as appropriate. Results: In EMA compared to HC and IGE we found: (1) higher blood oxygenation level-dependent (BOLD) signal related to the eye closure over the visual cortex, the posterior thalamus, and the network implicated in the motor control of eye closure, saccades, and eye pursuit movements; and (2) increments in the gray matter concentration at the visual cortex and thalamic pulvinar, whereas decrements were observed at the bilateral frontal eye field area. No BOLD differences were detected when comparing SWD in EMA and IGE. Interpretation: Results demonstrated altered anatomo-functional properties of the visual system in EMA. These abnormalities involve a circuit encompassing the occipital cortex and the cortical/subcortical systems physiologically involved in the motor control of eye closure and eye movements. Our work supports EMA as an epileptic condition with distinctive features and provides a contribution to its classification among epileptic syndromes

Deep brain stimulation of the ventralis oralis anterior thalamic nucleus is effective for dystonic tremor.

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