The sound of silence: Quantification of typical absence seizures by sonifying EEG signals from a custom-built wearable device.

OBJECTIVE: To develop and validate a method for long-term (24-h) objective quantification of absence seizures in the EEG of patients with childhood absence epilepsy (CAE) in their real home environment using a wearable device (waEEG), comparing automatic detection methods with auditory recognition after seizure sonification. METHODS: The waEEG recording was acquired with two scalp electrodes. Automatic analysis was performed using previously validated software (Persyst® 14) and then fully reviewed by an experienced clinical neurophysiologist. The EEG data were converted into an audio file in waveform format with a 60-fold time compression factor. The sonified EEG was listened to by three inexperienced observers and the number of seizures and the processing time required for each data set were recorded blind to other data. Quantification of seizures from the patient diary was also assessed. RESULTS: Eleven waEEG recordings from seven CAE patients with an average age of 8.18 ± 1.60 years were included. No differences in the number of seizures were found between the recordings using automated methods and expert audio assessment, with significant correlations between methods (ρ > .89, p < .001) and between observers (ρ > .96, p < .001). For the entire data set, the audio assessment yielded a sensitivity of .830 and a precision of .841, resulting in an F1 score of .835. SIGNIFICANCE: Auditory waEEG seizure detection by lay medical personnel provided similar accuracy to post-processed automatic detection by an experienced clinical neurophysiologist, but in a less time-consuming procedure and without the need for specialized resources. Sonification of long-term EEG recordings in CAE provides a user-friendly and cost-effective clinical workflow for quantifying seizures in clinical practice, minimizing human and technical constraints.

High incidence of early thalamic lesions in the Continuous Spike-Wave related with slow Sleep (CSWS).

OBJECTIVE: Continuous Spike-Wave during slow Sleep (CSWS) syndrome associates a clinically important neurocognitive regression with strong activation of non-REM sleep spikes. Its mechanisms remain unknown, but a contribution of rare perinatal thalamic injuries has been highlighted. We determine the incidence of such lesions in a cohort of CSWS patients. METHODS: N = 65 patients with CSWS and a control group (N = 51) were studied. Spikes were quantified in long-term ambulatory EEGs, brain Magnetic Ressonance Imaging (MRI) structural lesions were assessed and thalamic volumetry was performed. A neurocognitive scale was used to assess dysfunction. RESULTS: The most common etiologies in the control patients were not represented in the CSWS group. Structural lesions were detected in a minority of CSWS patients (25/53) but included a thalamic injury in the large majority (24/25). This ratio was 4/40 in controls. Lesions belonged to one of five types: 1. Circumscribed to the thalamus (N = 11); 2. Extending beyond the thalamus (N = 3); 3. Hypothalamic-Hamartomas (N = 4); 4. Periventricular-Leukomalacia (N = 4); 5. Hypoplasia-Polymicrogyria (N = 1). Most lesions were lateralized to one hemisphere, which in all cases corresponded to the lateralization of the CSWS. SIGNIFICANCE: Thalamic lesions are present in most CSWS patients with abnormal MRIs, supporting an important role in its genesis.

Visual word form area hyperexcitability associated with focal epileptiform activity in a case of reading epilepsy

Reading epilepsy recruits critical language-related areas, with synchronization and subsequent spreading of excitation in response to the epileptogenic stimulus. The mechanism by which possible generalized discharges result in the expression of bilateral or unilateral clinical symptoms remains controversial. The cortical and subcortical areas involved may constitute part of the normal reading network, such as the visual word form area (VWFA). A right-handed, 59-year-old man was diagnosed with epilepsy at the age of 15 after tonic-clonic seizures. Later, the patient described myoclonic jerks of the masticatory and perioral muscles while reading. A multimodal approach with magnetic resonance imaging and ambulatory and video-electroencephalogram was used for seizure characterization and source analysis. A left hemisphere spontaneous occipital-temporal epileptic focus, activated by reading, was observed, spreading broadly throughout frontal and temporal language networks. There was an abnormally increased cortical response to visual word presentation in comparison to pseudowords. Spatial localization of spike sources suggested a close association between the primary epileptic focus and the VWFA. This epileptiform activity seems to be selectively triggered at an early stage of lexical processing, with a functional connection between the epileptic network and the VWFA. This multimodal and functional connectivity approach could be helpful in determining the epileptic network in reading epilepsy.

EEG Microstates Predict Concurrent fMRI Dynamic Functional Connectivity States.

Brain functional connectivity measured by resting-state fMRI varies over multiple time scales, and recurrent dynamic functional connectivity (dFC) states have been identified. These have been found to be associated with different cognitive and pathological states, with potential as disease biomarkers, but their neuronal underpinnings remain a matter of debate. A number of recurrent microstates have also been identified in resting-state EEG studies, which are thought to represent the quasi-simultaneous activity of large-scale functional networks reflecting time-varying brain states. Here, we hypothesized that fMRI-derived dFC states may be associated with these EEG microstates. To test this hypothesis, we quantitatively assessed the ability of EEG microstates to predict concurrent fMRI dFC states in simultaneous EEG-fMRI data collected from healthy subjects at rest. By training a random forests classifier, we found that the four canonical EEG microstates predicted fMRI dFC states with an accuracy of 90%, clearly outperforming alternative EEG features such as spectral power. Our results indicate that EEG microstates analysis yields robust signatures of fMRI dFC states, providing evidence of the electrophysiological underpinnings of dFC while also further supporting that EEG microstates reflect the dynamics of large-scale brain networks.

Spatial and temporal dynamics of epileptic activity at sleep onset in the Encephalopathy with Status Epilepticus during slow sleep (ESES) after unilateral thalamic lesions.

OBJECTIVE: Encephalopathy with Status Epilepticus during slow Sleep (ESES) is a syndrome where neurocognitive impairment correlates with multifocal Electroencephalography (EEG) spikes increasing abruptly at sleep onset. Demonstration of a focal onset could provide important clues to unravel the mechanisms underlying the condition, but until know it has not been established. METHODS: We studied epileptic dynamics at sleep onset to assess its focal or diffuse features in five patients with perinatal thalamic hemorrhages lateralized to one hemisphere, using high resolution EEG. RESULTS: Dynamical functional connectivity revealed the information flow in the epileptic network and identified primary sources of outflow, equated with cortical spike sources. We found that spikes with important activation originate in restricted cortical areas of the hemisphere with the lesion, spreading widely and quickly at onset of N2 sleep stage. CONCLUSIONS: Perinatal thalamic lesions have the potential to induce, years later, a regional onset of epileptic activity with features of ESES in a cortex without apparent structural lesion. Most widespread spike activity in the scalp results from secondary propagation. SIGNIFICANCE: Perinatal thalamic lesions produce ESES with focal onset in a restricted cortical area of the hemisphere with the lesion, and prominent secondary propagation.

Regional White Matter Atrophy Correlates with Spike Activity in Encephalopathy Related to Status Epilepticus During Slow Sleep (ESES) After Early Thalamic Lesions.

Encephalopathy related to Status Epilepticus during slow Sleep (ESES) is an age-related, epileptic syndrome, which associates cognitive/behavioral disturbances with a peculiar pattern of spike activity. One promising line of research is the study of ESES in cases of early thalamic lesions. We studied 7 ESES patients with unilateral thalamic lesions using magnetic resonance imaging to assess regional white matter (WM) and thalamic nuclei volume differences, and long-term electroencephalogram recordings to localize the epileptogenic cortex. N170 event-related potentials were used to demonstrate the dysfunctional character of the WM abnormalities. Diffusion-weighted images in a subset of 4 patients were used to parcellate the thalamus and evaluate volume asymmetries, based on cortical connectivity. Large WM regional atrophy in the hemisphere with the thalamic lesion was associated with both cortical dysfunction and epileptic activity. A correlation was demonstrated between lesions in the pulvinar and the mediodorsal thalamic nuclei and WM atrophy of the corresponding cortical projection areas. We propose that these abnormalities are due to the widespread structural disconnection produced by the thalamic lesions associated to a yet unknown age-dependent factor. Further exploration of WM regional atrophy association with the spike activity in other etiologies could lend support to the cortical disconnection role in ESES genesis.

Interictal spike quantification in continuous spike-wave of sleep (CSWS): Clinical usefulness of a wearable EEG device.

INTRODUCTION: Continuous spike-wave of sleep (CSWS) syndrome is one of the most common epileptic encephalopathies of childhood. Because the associated cognitive/behavioral disturbances relate more to the amount of spike activity than of seizures, methods of spike quantification gained relevance in diagnosis and monitoring treatment. The conventional methodology for quantification of spike index (SI) relies on repeated full 10-20 long-term ambulatory electroencephalography (aEEG), which is both expensive and poorly tolerated. OBJECTIVE: The objectives of this study were to demonstrate the clinical value of repeated SI assessments in CSWS and to build and validate a wearable device allowing inexpensive and well-tolerated, repeated quantifications. METHODS: A group of N = 38 patients with CSWS were submitted to repeated SI quantifications based on aEEG, as seen fit by the medical clinical assistant. Responses to therapy with corticosteroids (N = 10), sulthiame (N = 7), and the ketogenic diet (N = 3) were monitored. We used a conventional method based on a semiautomatic template match spike search. The individual variability in time spans of days (N = 4) or months (N = 10) was assessed and used to determine the meaningful neurophysiological responses to the diverse therapies. A wearable device capable of recording 2 bipolar EEG channels for 24 h was used to simplify SI quantification. RESULTS: Corticosteroids produced the most powerful SI reduction, but a large individual variability in both amount and time of onset of clinical response with some patients exhibiting recurrence shortly after therapy. A more frequent sampling of SI would provide a more accurate follow-up, with clinical benefit. The comparison of the SI obtained from standard 10-20 electrodes and 2 bipolar EEG channel subsets in aEEG or between the 10-20 and simultaneous wearable recordings, demonstrated that the new method provides an accurate SI quantification. CONCLUSIONS: A wearable EEG device with 2 bipolar channels simplifies the process of obtaining repeated SI quantification allowing a more accurate follow-up of spike activity in the clinical setting.

Identification of epileptic brain states by dynamic functional connectivity analysis of simultaneous EEG-fMRI: a dictionary learning approach.

Most fMRI studies of the brain's intrinsic functional connectivity (FC) have assumed that this is static; however, it is now clear that it changes over time. This is particularly relevant in epilepsy, which is characterized by a continuous interchange between epileptic and normal brain states associated with the occurrence of epileptic activity. Interestingly, recurrent states of dynamic FC (dFC) have been found in fMRI data using unsupervised learning techniques, assuming either their sparse or non-sparse combination. Here, we propose an l1-norm regularized dictionary learning (l1-DL) approach for dFC state estimation, which allows an intermediate and flexible degree of sparsity in time, and demonstrate its application in the identification of epilepsy-related dFC states using simultaneous EEG-fMRI data. With this l1-DL approach, we aim to accommodate a potentially varying degree of sparsity upon the interchange between epileptic and non-epileptic dFC states. The simultaneous recording of the EEG is used to extract time courses representative of epileptic activity, which are incorporated into the fMRI dFC state analysis to inform the selection of epilepsy-related dFC states. We found that the proposed l1-DL method performed best at identifying epilepsy-related dFC states, when compared with two alternative methods of extreme sparsity (k-means clustering, maximum; and principal component analysis, minimum), as well as an l0-norm regularization framework (l0-DL), with a fixed amount of temporal sparsity. We further showed that epilepsy-related dFC states provide novel insights into the dynamics of epileptic networks, which go beyond the information provided by more conventional EEG-correlated fMRI analysis, and which were concordant with the clinical profile of each patient. In addition to its application in epilepsy, our study provides a new dFC state identification method of potential relevance for studying brain functional connectivity dynamics in general.

Evaluación de un gel antiséptico de aplicación intravaginal para pacientes con infecciones cervicovaginales multitratadas / Evaluation of an antiseptic gel of intravaginal application for multitreated patients for infectious cervicovaginitis

Resumen OBJETIVO: Evaluar la efectividad y seguridad de un gel intravaginal antiséptico, elaborado con agua electrolizada, en el tratamiento de infecciones cervicovaginales bacterianas, fúngicas, parasitarias o mixtas, y en el control de los síntomas típicos en pacientes multitratadas. MATERIALES y MÉTODOS: Estudio clínico, comparativo con el tratamiento convencional, de dos brazos, multicéntrico, al azar, con escalamiento de dosis efectuado en pacientes atendidas entre mayo de 2017 y mayo de 2018 en el servicio de Ginecología y Obstetricia del Hospital General de Ecatepec Las Américas, en el Estado de México y en el Centro Hospitalario Unión, de Colima. Grupo control: esquema convencional, antibiótico-antifúngico (7 días); grupos experimentales, gel antiséptico durante 3, 5 o 10 días. Seguimiento del pH vaginal, agente etiológico y síntomas. RESULTADOS: Se incluyeron 62 pacientes, con límites de edad de 18 y 42 años, con vaginitis bacteriana en 25 de 62, candidiasis 10 de 62, tricomoniasis 6 de 62 o infección mixta en 21 de 62, multitratadas. La aplicación del gel durante 5 o 10 días erradicó el agente etiológico en 14 de 15 y en 18 de 20 pacientes; con el tratamiento control lo lograron 8 de 14 pacientes (p = 0.021 y 0.030, respectivamente). El gel antiséptico aplicado durante 5 o 10 días fue casi 3 veces más eficaz que el tratamiento control para erradicar el agente infeccioso, eliminar los síntomas y normalizar el pH vaginal. CONCLUSIONES: El tratamiento durante 5 o 10 días con el gel antiséptico intravaginal fue casi 3 veces más efectivo que el convencional (antibiótico-antimicótico) en pacientes con cervicovaginitis infecciosa multitratada, útil en la eliminación de los síntomas típicos y bien tolerado.

Abstract OBJECTIVE: To evaluate the efficacy and safety of an intravaginal antiseptic gel, made of electrolyzed water, against bacterial, yeast, parasitic and mixed cervical infections, and to control typical symptoms in multi-treated patients. MATERIALS AND METHODS: Clinical study, comparative with conventional treatment, two arms, multicentric, randomized, with dose escalation carried out in patients attended between May 2017 and May 2018 in the gynecology and obstetrics service of the Hospital General de Ecatepec La Américas, in the Estado de Mexico and the Centro Hospitalario Unión, of Colima. Control group: conventional scheme, antibiotic-antifungal (7 days); Experimental groups, antiseptic gel for 3, 5 or 10 days. Monitoring of vaginal pH, etiologic agent and symptoms. RESULTS: 62 multi-treated patients (18-42 years old) were enrolled, presenting bacterial vaginosis 25/62, yeast infection 10/62, trichomoniasis 6/62 or mixed infection 21/62; bacteria and yeast). Treatment with antiseptic gel during 5 or 10 days eradicated etiological agent, respectively in 14/15 patients and 18/20 patients; control treatment did it in 8/14 patients (p = 0.021, p = 0.026, respectively). Additionally, gel treatment for 5 or 10 days was 3 times more effective than control treatment to eradicate the infection, control symptoms and to normalize vaginal pH. CONCLUSIONS: Intravaginal antiseptic gel (5-10 days) was almost 3 times more effective than conventional therapy (antibiotics/antimycotics) against multi-treated cervical infections; as well as useful to control typical symptoms and well tolerated.

EEG-Informed fMRI: A Review of Data Analysis Methods.

The simultaneous acquisition of electroencephalography (EEG) with functional magnetic resonance imaging (fMRI) is a very promising non-invasive technique for the study of human brain function. Despite continuous improvements, it remains a challenging technique, and a standard methodology for data analysis is yet to be established. Here we review the methodologies that are currently available to address the challenges at each step of the data analysis pipeline. We start by surveying methods for pre-processing both EEG and fMRI data. On the EEG side, we focus on the correction for several MR-induced artifacts, particularly the gradient and pulse artifacts, as well as other sources of EEG artifacts. On the fMRI side, we consider image artifacts induced by the presence of EEG hardware inside the MR scanner, and the contamination of the fMRI signal by physiological noise of non-neuronal origin, including a review of several approaches to model and remove it. We then provide an overview of the approaches specifically employed for the integration of EEG and fMRI when using EEG to predict the blood oxygenation level dependent (BOLD) fMRI signal, the so-called EEG-informed fMRI integration strategy, the most commonly used strategy in EEG-fMRI research. Finally, we systematically review methods used for the extraction of EEG features reflecting neuronal phenomena of interest.

EEG synchronization measures predict epilepsy-related BOLD-fMRI fluctuations better than commonly used univariate metrics.

OBJECTIVE: We hypothesize that the hypersynchronization associated with epileptic activity is best described by EEG synchronization measures, and propose to use these as predictors of epilepsy-related BOLD fluctuations. METHODS: We computed the phase synchronization index (PSI) and global field synchronization (GFS), within two frequency bands, a broadband (1-45 Hz) and a narrower band focused on the presence of epileptic activity (3-10 Hz). The associated epileptic networks were compared with those obtained using conventional unitary regressors and two power-weighted metrics (total power and root mean square frequency), on nine simultaneous EEG-fMRI datasets from four epilepsy patients, exhibiting inter-ictal epileptiform discharges (IEDs). RESULTS: The average PSI within 3-10 Hz achieved the best performance across several measures reflecting reliability in all datasets. The results were cross-validated through electrical source imaging of the IEDs. The applicability of PSI when no IEDs are recorded on the EEG was evaluated on three additional patients, yielding partially plausible networks in all cases. CONCLUSIONS: Epileptic networks can be mapped based on the EEG PSI metric within an IED-specific frequency band, performing better than commonly used EEG metrics. SIGNIFICANCE: This is the first study to investigate EEG synchronization measures as potential predictors of epilepsy-related BOLD fluctuations.

Anatomical and physiological basis of continuous spike-wave of sleep syndrome after early thalamic lesions.

OBJECTIVE: Early neonatal thalamic lesions account for about 14% of continuous spike-wave of sleep (CSWS) syndrome, representing the most common etiology in this epileptic encephalopathy in children, and promise useful insights into the pathophysiology of the disease. METHODS: We describe nine patients with unilateral neonatal thalamic lesions which progressed to CSWS. Longitudinal whole-night and high-density electroencephalograms (EEGs) were performed, as well as detailed imaging and clinical evaluation. Visual evoked potentials were used to probe cortical excitability. RESULTS: Thalamic volume loss ranged from 19% to 94%, predominantly on medial and dorsal nuclei and sparing the ventral thalamus. Lesions produced white matter loss and ventricle enlargement on the same hemisphere, which in four patients was associated with selective loss of thalamic-cortical fibers. Cortical thickness quantification failed to reveal hemispheric asymmetries. Impact on EEG rhythms was mild, with a volume-loss-related decrease in alpha power and preservation of sleep spindles. The sleep continuous spiking was lateralized to the hemisphere with the lesion. Visual cortex stimulation in five patients with posterior cortex spiking revealed an abnormal frequency-dependent excitability at 10-20Hz on the side of the lesion. SIGNIFICANCE: Unilateral selective thalamic-cortical disconnection is a common feature in our patients and is associated with both a focal pattern of CSWS and a pathological type of frequency-dependent excitability (peak: 10-20Hz). We propose that this excitability represents an abnormal synaptic plasticity previously described as the augmenting response. This synaptic plasticity has been described as absent in the corticocortical interactions in healthy experimental animals, emerging after ablation of the thalamus and producing a frequency-dependent potentiation with a peak at 10-20Hz. Because this response is potentiated by sleep states of reduced brainstem activation and by appropriate stimulating rhythms, such as sleep spindles, the simultaneous occurrence of these two factors in nonrapid-eye-movement sleep is proposed as an explanation for CSWS in our patients.

Physiological noise correction using ECG-derived respiratory signals for enhanced mapping of spontaneous neuronal activity with simultaneous EEG-fMRI.

The study of spontaneous brain activity based on BOLD-fMRI may be seriously compromised by the presence of signal fluctuations of non-neuronal origin, most prominently due to cardiac and respiratory mechanisms. Methods used for modeling and correction of the so-called physiological noise usually rely on the concurrent measurement of cardiac and respiratory signals. In simultaneous EEG-fMRI recordings, which are primarily aimed at the study of spontaneous brain activity, the electrocardiogram (ECG) is typically measured as part of the EEG setup but respiratory data are not generally available. Here, we propose to use the ECG-derived respiratory (EDR) signal estimated by Empirical Mode Decomposition (EMD) as a surrogate of the respiratory signal, for retrospective physiological noise correction of typical simultaneous EEG-fMRI data. A physiological noise model based on these physiological signals (P-PNM) complemented with fMRI-derived noise regressors was generated, and evaluated, for 17 simultaneous EEG-fMRI datasets acquired from a group of seven epilepsy patients imaged at 3T. The respiratory components of P-PNM were found to explain BOLD variance significantly in addition to the cardiac components, suggesting that the EDR signal was successfully extracted from the ECG, and P-PNM outperformed an image-based model (I-PNM) in terms of total BOLD variance explained. Further, the impact of the correction using P-PNM on fMRI mapping of patient-specific epileptic networks and the resting-state default mode network (DMN) was assessed in terms of sensitivity and specificity and, when compared with an ICA-based procedure and a standard pre-processing pipeline, P-PNM achieved the best performance. Overall, our results support the feasibility and utility of extracting physiological noise models of the BOLD signal resorting to ECG data exclusively, with substantial impact on the simultaneous EEG-fMRI mapping of resting-state networks, and, most importantly, epileptic networks where sensitivity and specificity are still limited.

Dynamics of epileptic activity in a peculiar case of childhood absence epilepsy and correlation with thalamic levels of GABA.

OBJECTIVES: Childhood absence epilepsy (CAE) is a syndrome with well-defined electroclinical features but unknown pathological basis. An increased thalamic tonic GABA inhibition has recently been discovered on animal models (Cope et al., 2009), but its relevance for human CAE is unproven. METHODS: We studied an 11-year-old boy, presenting the typical clinical features of CAE, but spike-wave discharges (SWD) restricted to one hemisphere. RESULTS: High-resolution EEG failed to demonstrate independent contralateral hemisphere epileptic activity. Consistently, simultaneous EEG-fMRI revealed the typical thalamic BOLD activation, associated with caudate and default mode network deactivation, but restricted to the hemisphere with SWD. Cortical BOLD activations were localized on the ipsilateral pars transverse. Magnetic resonance spectroscopy, using MEGA-PRESS, showed that the GABA/creatine ratio was 2.6 times higher in the hemisphere with SWD than in the unaffected one, reflecting a higher GABA concentration. Similar comparisons for the patient's occipital cortex and thalamus of a healthy volunteer yielded asymmetries below 25%. SIGNIFICANCE: In a clinical case of CAE with EEG and fMRI-BOLD manifestations restricted to one hemisphere, we found an associated increase in thalamic GABA concentration consistent with a role for this abnormality in human CAE.

Ballistocardiogram artifact correction taking into account physiological signal preservation in simultaneous EEG-fMRI.

The ballistocardiogram (BCG) artifact is currently one of the most challenging in the EEG acquired concurrently with fMRI, with correction invariably yielding residual artifacts and/or deterioration of the physiological signals of interest. In this paper, we propose a family of methods whereby the EEG is decomposed using Independent Component Analysis (ICA) and a novel approach for the selection of BCG-related independent components (ICs) is used (PROJection onto Independent Components, PROJIC). Three ICA-based strategies for BCG artifact correction are then explored: 1) BCG-related ICs are removed from the back-reconstruction of the EEG (PROJIC); and 2-3) BCG-related ICs are corrected for the artifact occurrences using an Optimal Basis Set (OBS) or Average Artifact Subtraction (AAS) framework, before back-projecting all ICs onto EEG space (PROJIC-OBS and PROJIC-AAS, respectively). A novel evaluation pipeline is also proposed to assess the methods performance, which takes into account not only artifact but also physiological signal removal, allowing for a flexible weighting of the importance given to physiological signal preservation. This evaluation is used for the group-level parameter optimization of each algorithm on simultaneous EEG-fMRI data acquired using two different setups at 3T and 7T. Comparison with state-of-the-art BCG correction methods showed that PROJIC-OBS and PROJIC-AAS outperformed the others when priority was given to artifact removal or physiological signal preservation, respectively, while both PROJIC-AAS and AAS were in general the best choices for intermediate trade-offs. The impact of the BCG correction on the quality of event-related potentials (ERPs) of interest was assessed in terms of the relative reduction of the standard error (SE) across trials: 26/66%, 32/62% and 18/61% were achieved by, respectively, PROJIC, PROJIC-OBS and PROJIC-AAS, for data collected at 3T/7T. Although more significant improvements were achieved at 7T, the results were qualitatively comparable for both setups, which indicate the wide applicability of the proposed methodologies and recommendations.

Objective selection of epilepsy-related independent components from EEG data.

BACKGROUND: Independent Component Analysis (ICA) is commonly used for the identification of sources of interest in electroencephalographic (EEG) data, but the selection of the relevant components remains an open issue depending on the specific application. NEW METHOD: We propose a novel approach for the objective selection of epilepsy-related independent components (ICs) from EEG data collected during functional Magnetic Resonance Imaging (fMRI) acquisitions, called PROJection onto Independent Components (PROJIC). Inter-ictal epileptiform discharges (IEDs) are identified on a reference EEG dataset collected outside the MRI scanner by an expert neurophysiologist, and the resulting average IED is projected onto the IC space of the EEG data collected simultaneously with fMRI. The power of the IED projection is then used to inform a k-means clustering algorithm of the ICs, allowing for the classification of epilepsy-related ICs. COMPARISON WITH EXISTING METHODS: The performance of PROJIC was compared with two methods previously proposed for the objective selection of EEG ICs of interest, which are based on the explicit similarity of the ICs with spatio-temporal templates of the events of interest, instead of the projection power. RESULTS: The proposed PROJIC method outperformed the others for both artificial and real data (19 datasets collected from 6 patients with drug-refractory focal epilepsy), with an average accuracy of 98.6%. CONCLUSIONS: The ability of our method to accurately and objectively select epilepsy-related ICs makes it an important contribution for simultaneous EEG-fMRI epilepsy studies, with potential applications in the analysis of event-related EEG activity more generally, and also in EEG artefact correction.

The Visual Word Form Area remains in the dominant hemisphere for language in late-onset left occipital lobe epilepsies: A postsurgery analysis of two cases.

Automatic recognition of words from letter strings is a critical processing step in reading that is lateralized to the left-hemisphere middle fusiform gyrus in the so-called Visual Word Form Area (VWFA). Surgical lesions in this location can lead to irreversible alexia. Very early left hemispheric lesions can lead to transfer of the VWFA to the nondominant hemisphere, but it is currently unknown if this capability is preserved in epilepsies developing after reading acquisition. In this study, we aimed to determine the lateralization of the VWFA in late-onset left inferior occipital lobe epilepsies and also the effect of surgical disconnection from the adjacent secondary visual areas. Two patients with focal epilepsies with onset near the VWFA underwent to surgery for epilepsy, with sparing of this area. Neuropsychology evaluations were performed before and after surgery, as well as quantitative evaluation of the speed of word reading. Comparison of the surgical localization of the lesion, with the BOLD activation associated with the contrast of words-strings, was performed, as well as a study of the associated main white fiber pathways using diffusion-weighted imaging. Neither of the patients developed alexia after surgery (similar word reading speed before and after surgery) despite the fact that the inferior occipital surgical lesions reached the neighborhood (less than 1cm) of the VWFA. Surgeries partly disconnected the VWFA from left secondary visual areas, suggesting that pathways connecting to the posterior visual ventral stream were severely affected but did not induce alexia. The anterior and superior limits of the resection suggest that the critical connection between the VWFA and the Wernicke's Angular Gyrus cortex was not affected, which is supported by the detection of this tract with probabilistic tractography. Left occipital lobe epilepsies developing after reading acquisition did not produce atypical localizations of the VWFA, even with foci in the close neighborhood. Surgery for occipital lobe epilepsy should take this into consideration, as well as the fact that disconnection from the left secondary visual areas may not produce alexia.

Characterisation and reduction of the EEG artefact caused by the helium cooling pump in the MR environment: validation in epilepsy patient data.

The EEG acquired simultaneously with fMRI is distorted by a number of artefacts related to the presence of strong magnetic fields, which must be reduced in order to allow for a useful interpretation and quantification of the EEG data. For the two most prominent artefacts, associated with magnetic field gradient switching and the heart beat, reduction methods have been developed and applied successfully. However, a number of artefacts related to the MR-environment can be found to distort the EEG data acquired even without ongoing fMRI acquisition. In this paper, we investigate the most prominent of those artefacts, caused by the Helium cooling pump, and propose a method for its reduction and respective validation in data collected from epilepsy patients. Since the Helium cooling pump artefact was found to be repetitive, an average template subtraction method was developed for its reduction with appropriate adjustments for minimizing the degradation of the physiological part of the signal. The new methodology was validated in a group of 15 EEG-fMRI datasets collected from six consecutive epilepsy patients, where it successfully reduced the amplitude of the artefact spectral peaks by 95 ± 2 % while the background spectral amplitude within those peaks was reduced by only -5 ± 4 %. Although the Helium cooling pump should ideally be switched off during simultaneous EEG-fMRI acquisitions, we have shown here that in cases where this is not possible the associated artefact can be effectively reduced in post processing.

The mismatch negativity (MMN) potential as a tool for the functional mapping of temporal lobe epilepsies.

Temporal lobe epilepsies are associated with cognitive dysfunctions in memory which are important clues currently used clinically for the lateralization of the epileptic focus in evaluations for epilepsy surgery. Because these lobes also contain the primary auditory cortex, the study of auditory evoked potentials (AEPs) is a candidate, not yet established, complementary method to characterize epilepsy-induced dysfunction. We aimed to establish the clinical usefulness of auditory evoked potentials for the study of pediatric symptomatic temporal lobe epilepsies. A group of 17 patients (ages 4-16) with symptomatic epilepsies undergoing evaluation for epilepsy surgery epilepsy was submitted to auditory evoked potentials using 35-channel scalp EEG recordings. A control group of 10 healthy volunteers was studied with the same protocol. The P100 and mismatch negativity (MMN) potential latencies and normalized amplitudes were studied. We also performed a voxel-based lesion-symptom mapping (VLSM) to determine the anatomical areas associated with changes in the AEPs. Eleven patients had temporal lobe epilepsy, three had frontal lobe epilepsy, and three had occipital lobe epilepsy. Latencies for the P100 were normal in 15/17 and in 11/17 for the MMN, with no consistent correlation with the epilepsy type. The MMN amplitude was abnormal in 7/17 patients, all with temporal lobe epilepsies (sensitivity of 64%). Of these patients, four had a decreased MMN associated with a Heschl's gyrus lesion in the VLSM, and three had an increased MMN associated with hippocampal lesion. No extratemporal epilepsy showed MMN amplitude abnormalities (specificity of 100%). The P100 amplitude was abnormal in 3/17, two with temporal and one with frontal lobe epilepsies. The auditory MMN has a high specificity but a low sensitivity for temporal lobe epilepsy in symptomatic pediatric epilepsies. Amplitude decreases of the MMN are associated with homolateral Heschl's gyrus lesions, and MMN increases with hippocampal lesions.

Neuropsychological abnormalities in children with the Panayiotopoulos syndrome point to parietal lobe dysfunction.

Panayiotopoulos syndrome (PS) is a common epilepsy syndrome associated with rare clinical seizures and unknown localization of the epileptogenic area. Despite findings of normal development in patients with PS, recent neuropsychological studies point to subtle and diverse cognitive impairments. No well-outlined hypothesis about the localization of the brain dysfunction responsible for these impairments has been proposed. We further explored the cognitive dysfunctions in PS and made inferences on the most likely anatomical localization of brain impairment. A group of 19 patients (aged 6-12) with PS was rated according to spike activity and lateralization. The patients were submitted to a neuropsychological evaluation to assess general intelligence, memory, language, visual-perceptual abilities, attention, and executive functions. Using 35-channel scalp EEG recordings, the N170 face-evoked event-related potential (ERP) was obtained to assess the functional integrity of the ventral pathway. All patients with PS showed normal IQ but subtle and consistent neurocognitive impairments. Namely, we found abnormalities in the copy task of the Rey-Osterrieth Complex Figure and in the Narrative Memory Test. There was no correlation between neuropsychological impairments with spike activity and hemispheric spike lateralization. The N170 ERP was normal in all patients except for one. Our neuropsychological findings demonstrate impairments in visual-perceptual abilities and in semantic processing. These findings, paired with the absence of occipital lobe dysfunction in all neuropsychological studies of PS performed to this date, support the existence of parietal lobe dysfunction.